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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Review Article

Molecular Bases of Protein Antigenicity and Determinants of Immunogenicity, Anergy, and Mitogenicity

Author(s): David Pedroza-Escobar*, Irais Castillo-Maldonado, Tania González-Cortés, Dealmy Delgadillo-Guzmán, Pablo Ruíz-Flores, Jorge Haro Santa Cruz, Perla-Karina Espino-Silva, Erika Flores-Loyola, Agustina Ramirez-Moreno, Joaquín Avalos-Soto, Miguel-Ángel Téllez-López, Sergio-Everardo Velázquez-Gauna, Rubén García-Garza, Rubén Daniel Arellano Pérez Vertti and Cristian Torres-León

Volume 30, Issue 9, 2023

Published on: 03 October, 2023

Page: [719 - 733] Pages: 15

DOI: 10.2174/0929866530666230907093339

Price: $65

Abstract

Background: The immune system is able to recognize substances that originate from inside or outside the body and are potentially harmful. Foreign substances that bind to immune system components exhibit antigenicity and are defined as antigens. The antigens exhibiting immunogenicity can induce innate or adaptive immune responses and give rise to humoral or cell-mediated immunity. The antigens exhibiting mitogenicity can cross-link cell membrane receptors on B and T lymphocytes leading to cell proliferation. All antigens vary greatly in physicochemical features such as biochemical nature, structural complexity, molecular size, foreignness, solubility, and so on.

Objective: Thus, this review aims to describe the molecular bases of protein-antigenicity and those molecular bases that lead to an immune response, lymphocyte proliferation, or unresponsiveness.

Conclusion: The epitopes of an antigen are located in surface areas; they are about 880-3,300 Da in size. They are protein, carbohydrate, or lipid in nature. Soluble antigens are smaller than 1 nm and are endocytosed less efficiently than particulate antigens. The more the structural complexity of an antigen increases, the more the antigenicity increases due to the number and variety of epitopes. The smallest immunogens are about 4,000-10,000 Da in size. The more phylogenetically distant immunogens are from the immunogen-recipient, the more immunogenicity increases. Antigens that are immunogens can trigger an innate or adaptive immune response. The innate response is induced by antigens that are pathogen-associated molecular patterns. Exogenous antigens, T Dependent or T Independent, induce humoral immunogenicity. TD protein-antigens require two epitopes, one sequential and one conformational to induce antibodies, whereas, TI non-protein-antigens require only one conformational epitope to induce low-affinity antibodies. Endogenous protein antigens require only one sequential epitope to induce cell-mediated immunogenicity.

Keywords: Antigen, hapten, immunogen, mitogen, antigenicity, anergy, immunogenicity, mitogenicity.

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[1]
Abbas, A.K.; Lichtman, A.H.; Pillai, S. Cellular and molecular immunology, 9th ed; Elsevier Science: Boston, MA, 2018.
[2]
Kennelly, P.J.; Botham, K.M.; McGuinness, O.P.; Rodwell, V.W.; Weill, P. Harper’s Illustrated Biochemistry; McGraw Hill: New York, 2023.
[3]
Castillo-Maldonado, I.; Pedroza-Escobar, D.; Molina-Ramírez, B.; Cabral-Hipólito, N.; Delgadillo-Guzmán, D.; Meza-Velázquez, R.; Ramírez-Moreno, A.; Flores-Loyola, E.; Ruíz-Flores, P.; Cruz, J.H-S.; Espino-Silva, P-K.; Avalos-Soto, J.; Téllez-López, M-Á.; Vertti, R.D.A.P.; Rosales-González, M-G. Tannic acid, as a structural moiety coupled to a protein antigen, exhibiting a molecular-structure adjuvant activity for antibody specificity enhancement. Protein Pept. Lett., 2022, 29(11), 925-936.
[http://dx.doi.org/10.2174/0929866529666220902152147] [PMID: 36056859]
[4]
Sattler, S. The role of the immune system beyond the fight against infection. Adv. Exp. Med. Biol., 2017, 1003, 3-14.
[http://dx.doi.org/10.1007/978-3-319-57613-8_1] [PMID: 28667551]
[5]
Yatim, K.M.; Lakkis, F.G. A brief journey through the immune system. Clin. J. Am. Soc. Nephrol., 2015, 10(7), 1274-1281.
[http://dx.doi.org/10.2215/CJN.10031014] [PMID: 25845377]
[6]
Pradeu, T.; Du Pasquier, L. Immunological memory: What’s in a name? Immunol. Rev., 2018, 283(1), 7-20.
[http://dx.doi.org/10.1111/imr.12652] [PMID: 29664563]
[7]
Netea, M.G.; Schlitzer, A.; Placek, K.; Joosten, L.A.B.; Schultze, J.L. Innate and adaptive immune memory: An evolutionary continuum in the host’s response to pathogens. Cell Host Microbe, 2019, 25(1), 13-26.
[http://dx.doi.org/10.1016/j.chom.2018.12.006] [PMID: 30629914]
[8]
Irais, C.M.; María-de-la-Luz, S.G.; Dealmy, D.G.; Agustina, R.M.; Nidia, C.H.; Mario-Alberto, R.G.; Luis-Benjamín, S.G.; María-del-Carmen, V.M.; David, P.E. Plant phenolics as pathogen-carrier immunogenicity modulator haptens. Curr. Pharm. Biotechnol., 2020, 21(10), 897-905.
[http://dx.doi.org/10.2174/1389201021666200121130313] [PMID: 31965941]
[9]
Pishesha, N.; Harmand, T.J.; Ploegh, H.L. A guide to antigen processing and presentation. Nat. Rev. Immunol., 2022, 22(12), 751-764.
[http://dx.doi.org/10.1038/s41577-022-00707-2] [PMID: 35418563]
[10]
Lousberg, E.L.; Diener, K.R.; Fraser, C.K.; Phipps, S.; Foster, P.S.; Chen, W.; Uematsu, S.; Akira, S.; Robertson, S.A.; Brown, M.P.; Hayball, J.D. Antigen-specific T-cell responses to a recombinant fowlpox virus are dependent on MyD88 and interleukin-18 and independent of Toll-like receptor 7 (TLR7)- and TLR9-mediated innate immune recognition. J. Virol., 2011, 85(7), 3385-3396.
[http://dx.doi.org/10.1128/JVI.02000-10] [PMID: 21248035]
[11]
Kapingidza, A.B.; Kowal, K.; Chruszcz, M. Antigen-antibody complexes. Subcell. Biochem., 2020, 94, 465-497.
[http://dx.doi.org/10.1007/978-3-030-41769-7_19] [PMID: 32189312]
[12]
Solouki, S.; Huang, W.; Elmore, J.; Limper, C.; Huang, F.; August, A. TCR signal strength and antigen affinity regulate CD8+ memory T cells. J. Immunol., 2020, 205(5), 1217-1227.
[http://dx.doi.org/10.4049/jimmunol.1901167] [PMID: 32759295]
[13]
Tang, L. Sequencing BCR–antigen interactions. Nat. Methods, 2020, 17(2), 129.
[http://dx.doi.org/10.1038/s41592-020-0749-4] [PMID: 32020094]
[14]
Grant, C.F.J.; Lefevre, E.A.; Carr, B.V.; Prentice, H.; Gubbins, S.; Pollard, A.J.; Charreyre, C.; Charleston, B. Assessment of T-dependent and T-independent immune responses in cattle using a B cell ELISPOT assay. Vet. Res., 2012, 43(1), 68.
[http://dx.doi.org/10.1186/1297-9716-43-68] [PMID: 23050495]
[15]
Jawa, V.; Terry, F.; Gokemeijer, J.; Mitra-Kaushik, S.; Roberts, B.J.; Tourdot, S.; De Groot, A.S. T-cell dependent immunogenicity of protein therapeutics pre-clinical assessment and mitigation-updated consensus and review 2020. Front. Immunol., 2020, 11, 1301.
[http://dx.doi.org/10.3389/fimmu.2020.01301] [PMID: 32695107]
[16]
Liu, X.; Zhao, Y.; Qi, H. T-independent antigen induces humoral memory through germinal centers. J. Exp. Med., 2022, 219(3), e20210527.
[http://dx.doi.org/10.1084/jem.20210527] [PMID: 35019947]
[17]
Alsalamah, M.; Vong, L.; Cimpean, L.; Dadi, H. Establishing reference ranges for lymphocyte proliferation responses to phytohemagglutinin in patients with T cell dysfunction. LymphoSign J., 2019, 6(1), 26-30.
[http://dx.doi.org/10.14785/lymphosign-2019-0002]
[18]
Abad-Fuentes, A.; Agulló, C.; López-Puertollano, D.; Navarro-Fuertes, I.; Abad-Somovilla, A.; Mercader, J.V. Alternative hapten design for zearalenone immunoreagent generation. Toxins, 2022, 14(3), 185.
[http://dx.doi.org/10.3390/toxins14030185] [PMID: 35324682]
[19]
Breberina, L.M.; Zlatović, M.V.; Nikolić, M.R.; Stojanović, S.Đ. Computational analysis of non-covalent interactions in phycocyanin subunit interfaces. Mol. Inform., 2019, 38(11-12), 1800145.
[http://dx.doi.org/10.1002/minf.201800145] [PMID: 31535472]
[20]
Raucci, R.; Laine, E.; Carbone, A. Local interaction signal analysis predicts protein-protein binding affinity. Structure, 2018, 26(6), 905-915.e4.
[http://dx.doi.org/10.1016/j.str.2018.04.006] [PMID: 29779789]
[21]
Chan, A.M.; Goodis, C.C.; Pommier, E.G.; Fletcher, S. Recent applications of covalent chemistries in protein–protein interaction inhibitors. RSC Med. Chem., 2022, 13(8), 921-928.
[http://dx.doi.org/10.1039/D2MD00112H] [PMID: 36092144]
[22]
Sethu, S.; Govindappa, K.; Alhaidari, M.; Pirmohamed, M.; Park, K.; Sathish, J. Immunogenicity to biologics: Mechanisms, prediction and reduction. Arch. Immunol. Ther. Exp., 2012, 60(5), 331-344.
[http://dx.doi.org/10.1007/s00005-012-0189-7] [PMID: 22930363]
[23]
Li, D.; Wu, M. Pattern recognition receptors in health and diseases. Signal Transduct. Target. Ther., 2021, 6(1), 291.
[http://dx.doi.org/10.1038/s41392-021-00687-0] [PMID: 34344870]
[24]
Zindel, J.; Kubes, P. DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation. Annu. Rev. Pathol., 2020, 15(1), 493-518.
[http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032847] [PMID: 31675482]
[25]
Odales, J.; Guzman Valle, J.; Martínez-Cortés, F.; Manoutcharian, K. Immunogenic properties of immunoglobulin superfamily members within complex biological networks. Cell. Immunol., 2020, 358, 104235.
[http://dx.doi.org/10.1016/j.cellimm.2020.104235] [PMID: 33137645]
[26]
Chen, Z.; Wang, J.H. How the signaling crosstalk of B cell receptor (BCR) and co-receptors regulates antibody class switch recombination: A new perspective of checkpoints of BCR signaling. Front. Immunol., 2021, 12, 663443.
[http://dx.doi.org/10.3389/fimmu.2021.663443] [PMID: 33841447]
[27]
Cyster, J.G.; Allen, C.D.C. B cell responses: Cell interaction dynamics and decisions. Cell, 2019, 177(3), 524-540.
[http://dx.doi.org/10.1016/j.cell.2019.03.016] [PMID: 31002794]
[28]
Ghraichy, M.; Galson, J.D.; Kelly, D.F.; Trück, J. B-cell receptor repertoire sequencing in patients with primary immunodeficiency: A review. Immunology, 2018, 153(2), 145-160.
[http://dx.doi.org/10.1111/imm.12865] [PMID: 29140551]
[29]
Zhang, S.; Yang, T.; Liu, X.; Yang, J.; Zheng, X. Antibody repertoire sequencing analysis. Acta Biochim. Biophys. Sin., 2022, 54(6), 864-873.
[http://dx.doi.org/10.3724/abbs.2022062] [PMID: 35713313]
[30]
Foth, S.; Völkel, S.; Bauersachs, D.; Zemlin, M.; Skevaki, C. T cell repertoire during ontogeny and characteristics in inflammatory disorders in adults and childhood. Front. Immunol., 2021, 11, 611573.
[http://dx.doi.org/10.3389/fimmu.2020.611573] [PMID: 33633732]
[31]
Migalska, M.; Sebastian, A.; Radwan, J. Profiling of the TCRβ repertoire in non-model species using high-throughput sequencing. Sci. Rep., 2018, 8(1), 11613.
[http://dx.doi.org/10.1038/s41598-018-30037-0] [PMID: 30072736]
[32]
Perniola, R. Twenty Years of AIRE. Front. Immunol., 2018, 9, 98.
[http://dx.doi.org/10.3389/fimmu.2018.00098] [PMID: 29483906]
[33]
Melo-Lima, B.L.; Poras, I.; Passos, G.A.; Carosella, E.D.; Donadi, E.A.; Moreau, P. The Autoimmune Regulator (Aire) transactivatesHLA-G gene expression in thymic epithelial cells. Immunology, 2019, 158(2), 121-135.
[http://dx.doi.org/10.1111/imm.13099] [PMID: 31322727]
[34]
Sun, P.; Guo, S.; Sun, J.; Tan, L.; Lu, C.; Ma, Z. Advances in in silico B-cell epitope prediction. Curr. Top. Med. Chem., 2019, 19(2), 105-115.
[http://dx.doi.org/10.2174/1568026619666181130111827] [PMID: 30499399]
[35]
Mahapatra, S.R.; Dey, J.; Kaur, T.; Sarangi, R.; Bajoria, A.A.; Kushwaha, G.S.; Misra, N.; Suar, M. Immunoinformatics and molecular docking studies reveal a novel Multi-Epitope peptide vaccine against pneumonia infection. Vaccine, 2021, 39(42), 6221-6237.
[http://dx.doi.org/10.1016/j.vaccine.2021.09.025] [PMID: 34556364]
[36]
Farrow, B.; Wong, M.; Malette, J.; Lai, B.; Deyle, K.M.; Das, S.; Nag, A.; Agnew, H.D.; Heath, J.R. Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin. Angew. Chem. Int. Ed., 2015, 54(24), 7114-7119.
[http://dx.doi.org/10.1002/anie.201502451] [PMID: 25925721]
[37]
Gallichotte, E.N.; Baric, T.J.; Yount, B.L., Jr; Widman, D.G.; Durbin, A.; Whitehead, S.; Baric, R.S.; de Silva, A.M. Human dengue virus serotype 2 neutralizing antibodies target two distinct quaternary epitopes. PLoS Pathog., 2018, 14(2), e1006934.
[http://dx.doi.org/10.1371/journal.ppat.1006934] [PMID: 29481552]
[38]
Collins, M.H.; Tu, H.A.; Gimblet-Ochieng, C.; Liou, G.J.A.; Jadi, R.S.; Metz, S.W.; Thomas, A.; McElvany, B.D.; Davidson, E.; Doranz, B.J.; Reyes, Y.; Bowman, N.M.; Becker-Dreps, S.; Bucardo, F.; Lazear, H.M.; Diehl, S.A.; de Silva, A.M. Human antibody response to Zika targets type-specific quaternary structure epitopes. JCI Insight, 2019, 4(8), e124588.
[http://dx.doi.org/10.1172/jci.insight.124588] [PMID: 30996133]
[39]
Burster, T.; Macmillan, H.; Hou, T.; Boehm, B.O.; Mellins, E.D. Cathepsin G: Roles in antigen presentation and beyond. Mol. Immunol., 2010, 47(4), 658-665.
[http://dx.doi.org/10.1016/j.molimm.2009.10.003] [PMID: 19910052]
[40]
Jurewicz, M.M.; Stern, L.J. Class II MHC antigen processing in immune tolerance and inflammation. Immunogenetics, 2019, 71(3), 171-187.
[http://dx.doi.org/10.1007/s00251-018-1095-x] [PMID: 30421030]
[41]
Wang, Y.; Liu, J.; Burrows, P.D.; Wang, J.Y. B cell development and maturation. Adv. Exp. Med. Biol., 2020, 1254, 1-22.
[http://dx.doi.org/10.1007/978-981-15-3532-1_1] [PMID: 32323265]
[42]
Mond, J.; Vos, Q.; Lees, A.; Snapper, C.M. T cell independent antigens. Curr. Opin. Immunol., 1995, 7(3), 349-354.
[http://dx.doi.org/10.1016/0952-7915(95)80109-X] [PMID: 7546399]
[43]
Villar, R.F.; Patel, J.; Weaver, G.C.; Kanekiyo, M.; Wheatley, A.K.; Yassine, H.M.; Costello, C.E.; Chandler, K.B.; McTamney, P.M.; Nabel, G.J.; McDermott, A.B.; Mascola, J.R.; Carr, S.A.; Lingwood, D. Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation. Sci. Rep., 2016, 6(1), 36298.
[http://dx.doi.org/10.1038/srep36298] [PMID: 27796362]
[44]
Vos, Q.; Lees, A.; Wu, Z.Q.; Snapper, C.M.; Mond, J.J. B-cell activation by T-cell-independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms. Immunol. Rev., 2000, 176(1), 154-170.
[http://dx.doi.org/10.1034/j.1600-065X.2000.00607.x] [PMID: 11043775]
[45]
Murata, S.; Takahama, Y.; Kasahara, M.; Tanaka, K. The immunoproteasome and thymoproteasome: Functions, evolution and human disease. Nat. Immunol., 2018, 19(9), 923-931.
[http://dx.doi.org/10.1038/s41590-018-0186-z] [PMID: 30104634]
[46]
Calis, J.J.A.; Maybeno, M.; Greenbaum, J.A.; Weiskopf, D.; De Silva, A.D.; Sette, A.; Keşmir, C.; Peters, B. Properties of MHC class I presented peptides that enhance immunogenicity. PLOS Comput. Biol., 2013, 9(10), e1003266.
[http://dx.doi.org/10.1371/journal.pcbi.1003266] [PMID: 24204222]
[47]
Taniuchi, I. CD4 helper and CD8 cytotoxic T cell differentiation. Annu. Rev. Immunol., 2018, 36(1), 579-601.
[http://dx.doi.org/10.1146/annurev-immunol-042617-053411] [PMID: 29677476]
[48]
Cambier, J.C.; Gauld, S.B.; Merrell, K.T.; Vilen, B.J. B-cell anergy: From transgenic models to naturally occurring anergic B cells? Nat. Rev. Immunol., 2007, 7(8), 633-643.
[http://dx.doi.org/10.1038/nri2133] [PMID: 17641666]
[49]
Rosenspire, A.J.; Chen, K.; Anergic, B. Anergic B cells: Precarious on-call warriors at the nexus of autoimmunity and false-flagged pathogens. Front. Immunol., 2015, 6, 580.
[http://dx.doi.org/10.3389/fimmu.2015.00580] [PMID: 26635794]
[50]
Schwartz, R.H. T cell anergy. Annu. Rev. Immunol., 2003, 21(1), 305-334.
[http://dx.doi.org/10.1146/annurev.immunol.21.120601.141110] [PMID: 12471050]
[51]
Valdor, R.; Macian, F. Mechanisms of self-inactivation in anergic T cells. Inmunologia, 2010, 29(1), 20-33.
[http://dx.doi.org/10.1016/S0213-9626(10)70008-1]
[52]
Wimer, B.M.; Mann, P.L. Mitogen information summaries. Cancer Biother. Radiopharm., 2002, 17(5), 569-597.
[http://dx.doi.org/10.1089/108497802760804808] [PMID: 12470427]
[53]
Nam, J.H.; Cha, B.; Park, J.Y.; Abekura, F.; Kim, C.H.; Kim, J.R. Mitogen-induced interferon gamma production in human whole blood: The effect of heat and cations. Curr. Pharm. Biotechnol., 2019, 20(7), 562-572.
[http://dx.doi.org/10.2174/1389201020666190528093432] [PMID: 31132974]
[54]
Yaglova, N.V.; Tsomartova, E.S.; Obernikhin, S.S.; Ivanova, M.Y.; Chereshneva, E.V.; Muhamedova, S.G.; Lomanovskaya, T.A.; Yaglov, V.V. Developmental exposure to low doses of dichlorodiphenyltrichloroethane impairs proliferative response of thymic lymphocytes to Concanavalin A in rats. Heliyon, 2020, 6(3), e03608.
[http://dx.doi.org/10.1016/j.heliyon.2020.e03608] [PMID: 32195406]
[55]
Yoshihara, R.; Aoyama, E.; Kadota, Y.; Kawai, S.; Goto, T.; Zhong, M.; Gohda, E. Differentiation of murine B cells induced by chondroitin sulfate B. Cell. Immunol., 2007, 250(1-2), 14-23.
[http://dx.doi.org/10.1016/j.cellimm.2007.12.002] [PMID: 18206137]
[56]
Horie, K.; Hoshi, H.; Hamano, K.; Kaneko, T. Morphological changes in the mouse popliteal lymph node after local injection of dextran sulfate. Tohoku J. Exp. Med., 1994, 172(3), 175-193.
[http://dx.doi.org/10.1620/tjem.172.175] [PMID: 8073429]
[57]
Morimoto, J.; Sarkar, M.; Kenrick, S.; Kodadek, T. Dextran as a generally applicable multivalent scaffold for improving immunoglobulin-binding affinities of peptide and peptidomimetic ligands. Bioconjug. Chem., 2014, 25(8), 1479-1491.
[http://dx.doi.org/10.1021/bc500226j] [PMID: 25073654]
[58]
Saylor, K.; Gillam, F.; Lohneis, T.; Zhang, C. Designs of antigen structure and composition for improved protein-based vaccine efficacy. Front. Immunol., 2020, 11, 283.
[http://dx.doi.org/10.3389/fimmu.2020.00283] [PMID: 32153587]
[59]
Zinsli, L.V.; Stierlin, N.; Loessner, M.J.; Schmelcher, M. Deimmunization of protein therapeutics - Recent advances in experimental and computational epitope prediction and deletion. Comput. Struct. Biotechnol. J., 2021, 19, 315-329.
[http://dx.doi.org/10.1016/j.csbj.2020.12.024] [PMID: 33425259]
[60]
Sadegh-Nasseri, S.; Kim, A. Selection of immunodominant epitopes during antigen processing is hierarchical. Mol. Immunol., 2019, 113, 115-119.
[http://dx.doi.org/10.1016/j.molimm.2018.08.011] [PMID: 30146122]
[61]
Wang, G.; Wan, H.; Jian, X.; Li, Y.; Ouyang, J.; Tan, X.; Zhao, Y.; Lin, Y.; Xie, L. INeo-Epp: A novel T-Cell HLA Class-I immunogenicity or neoantigenic epitope prediction method based on sequence-related amino acid features. BioMed Res. Int., 2020, 2020, 1-12.
[http://dx.doi.org/10.1155/2020/5798356] [PMID: 32626747]
[62]
Tang, S.; Li, J.; Huang, G.; Yan, L. Predicting protein surface property with its surface hydrophobicity. Protein Pept. Lett., 2021, 28(8), 938-944.
[http://dx.doi.org/10.2174/18755305MTE0oNDQ54] [PMID: 33618636]
[63]
Essentials of Glycobiology, 3rd ed.; Varki, A.; Cummings, R.D.; Esko, J.D.; Stanley, P.; Hart, G.W.; Aebi, M.; Darvill, A.G.; Kinoshita, T.; Packer, N.H.; Prestegard, J.H.; Schnaar, R.L.; Seeberger, P.H., Eds.; Cold Spring Harbor Laboratory Press: NY: Cold Spring Harbor (NY), 2015.
[64]
Cummings, J.H.; Stephen, A.M. Carbohydrate terminology and classification. Eur. J. Clin. Nutr., 2007, 61(S1), S5-S18.
[http://dx.doi.org/10.1038/sj.ejcn.1602936] [PMID: 17992187]
[65]
Vecchiarelli, A. Fungal capsular polysaccharide and T-cell suppression: The hidden nature of poor immunogenicity. Crit. Rev. Immunol., 2007, 27(6), 547-557.
[http://dx.doi.org/10.1615/CritRevImmunol.v27.i6.50] [PMID: 18197800]
[66]
Khatun, F.; Stephenson, R.J.; Toth, I. An overview of structural features of antibacterial glycoconjugate vaccines that influence their immunogenicity. Chemistry, 2017, 23(18), 4233-4254.
[http://dx.doi.org/10.1002/chem.201603599] [PMID: 28097690]
[67]
Heimburg-Molinaro, J.; Rittenhouse-Olson, K. Development and characterization of antibodies to carbohydrate antigens. Methods Mol. Biol., 2009, 534, 341-357.
[http://dx.doi.org/10.1007/978-1-59745-022-5_24] [PMID: 19277540]
[68]
Fahy, E.; Cotter, D.; Sud, M.; Subramaniam, S. Lipid classification, structures and tools. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2011, 1811(11), 637-647.
[http://dx.doi.org/10.1016/j.bbalip.2011.06.009] [PMID: 21704189]
[69]
Fahy, E.; Subramaniam, S.; Brown, H.A.; Glass, C.K.; Merrill, A.H., Jr; Murphy, R.C.; Raetz, C.R.H.; Russell, D.W.; Seyama, Y.; Shaw, W.; Shimizu, T.; Spener, F.; van Meer, G.; VanNieuwenhze, M.S.; White, S.H.; Witztum, J.L.; Dennis, E.A. A comprehensive classification system for lipids. J. Lipid Res., 2005, 46(5), 839-861.
[http://dx.doi.org/10.1194/jlr.E400004-JLR200] [PMID: 15722563]
[70]
Bartlett, S.; Skwarczynski, M.; Toth, I. Lipids as activators of innate immunity in peptide vaccine delivery. Curr. Med. Chem., 2020, 27(17), 2887-2901.
[http://dx.doi.org/10.2174/0929867325666181026100849] [PMID: 30362416]
[71]
Ciesielska, A.; Matyjek, M.; Kwiatkowska, K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell. Mol. Life Sci., 2021, 78(4), 1233-1261.
[http://dx.doi.org/10.1007/s00018-020-03656-y] [PMID: 33057840]
[72]
Jez, J.M. Revisiting protein structure, function, and evolution in the genomic era. J. Invertebr. Pathol., 2017, 142, 11-15.
[http://dx.doi.org/10.1016/j.jip.2016.07.013] [PMID: 27486121]
[73]
Balchin, D.; Hayer-Hartl, M.; Hartl, F.U. in vivo aspects of protein folding and quality control. Science, 2016, 353(6294), aac4354.
[http://dx.doi.org/10.1126/science.aac4354] [PMID: 27365453]
[74]
Hesch, R.D. Classification of cell receptors. Curr. Top. Pathol., 1991, 83, 13-51.
[http://dx.doi.org/10.1007/978-3-642-75515-6_2] [PMID: 1848803]
[75]
Wilson, I.A.; Stanfield, R.L. 50 Years of structural immunology. J. Biol. Chem., 2021, 296, 100745.
[http://dx.doi.org/10.1016/j.jbc.2021.100745] [PMID: 33957119]
[76]
Keyt, B.A.; Baliga, R.; Sinclair, A.M.; Carroll, S.F.; Peterson, M.S. Structure, function, and therapeutic use of IgM antibodies. Antibodies, 2020, 9(4), 53.
[http://dx.doi.org/10.3390/antib9040053] [PMID: 33066119]
[77]
Harlow, E.; Lane, D. Unmasking hidden epitopes with proteases. CSH Protoc., 2006, 2006(4), pdb.prot4528.
[http://dx.doi.org/10.1101/pdb.prot4528]
[78]
Siqueira Silva, M.; Moreira Tavares, A.P.; Leomil Coelho, L.F.; Morganti Ferreira Dias, L.E.; Chura-Chambi, R.M.; Guimarães da Fonseca, F.; Ferreira Sales, M.G.; Costa Figueiredo, E. Rational selection of hidden epitopes for a molecularly imprinted electrochemical sensor in the recognition of heat-denatured dengue NS1 protein. Biosens. Bioelectron., 2021, 191, 113419.
[http://dx.doi.org/10.1016/j.bios.2021.113419] [PMID: 34144470]
[79]
Zhang, Q.; Wise, K.S. Molecular basis of size and antigenic variation of a Mycoplasma hominis adhesin encoded by divergent vaa genes. Infect. Immun., 1996, 64(7), 2737-2744.
[http://dx.doi.org/10.1128/iai.64.7.2737-2744.1996] [PMID: 8698503]
[80]
Bachmann, M.F.; Jennings, G.T. Vaccine delivery: A matter of size, geometry, kinetics and molecular patterns. Nat. Rev. Immunol., 2010, 10(11), 787-796.
[http://dx.doi.org/10.1038/nri2868] [PMID: 20948547]
[81]
Zhang, F.; Lu, Y.J.; Malley, R. Multiple antigen-presenting system (MAPS) to induce comprehensive B- and T-cell immunity. Proc. Natl. Acad. Sci., 2013, 110(33), 13564-13569.
[http://dx.doi.org/10.1073/pnas.1307228110] [PMID: 23898212]
[82]
Zimecki, M.; Webb, D.R. The influence of molecular weight on immunogenicity and suppressor cells in the immune response to polyvinylpyrollidone. Clin. Immunol. Immunopathol., 1978, 9(1), 75-79.
[http://dx.doi.org/10.1016/0090-1229(78)90123-X] [PMID: 336252]
[83]
Crumpton, M.J. Protein antigens: The molecular bases of antigenicity and immunogenicity. In: The Antigens; Sela, M., Ed.; Academic Press, 1974; pp. 1-78.
[http://dx.doi.org/10.1016/B978-0-12-635502-4.50008-4]
[84]
Al Qaraghuli, M.M.; Palliyil, S.; Broadbent, G.; Cullen, D.C.; Charlton, K.A.; Porter, A.J. Defining the complementarities between antibodies and haptens to refine our understanding and aid the prediction of a successful binding interaction. BMC Biotechnol., 2015, 15(1), 99.
[http://dx.doi.org/10.1186/s12896-015-0217-x] [PMID: 26498921]
[85]
Du, Q.S.; Wei, Y.T.; Pang, Z.W.; Chou, K.C.; Huang, R.B. Predicting the affinity of epitope-peptides with class I MHC molecule HLA-A*0201: An application of amino acid-based peptide prediction. Protein Eng. Des. Sel., 2007, 20(9), 417-423.
[http://dx.doi.org/10.1093/protein/gzm036] [PMID: 17681974]
[86]
Wieczorek, M.; Abualrous, E.T.; Sticht, J.; Álvaro-Benito, M.; Stolzenberg, S.; Noé, F.; Freund, C. Major Histocompatibility Complex (MHC) class I and MHC Class II proteins: Conformational plasticity in antigen presentation. Front. Immunol., 2017, 8, 292.
[http://dx.doi.org/10.3389/fimmu.2017.00292] [PMID: 28367149]
[87]
van den Berg, H.A.; Rand, D.A. Foreignness as a matter of degree: The relative immunogenicity of peptide/MHC ligands. J. Theor. Biol., 2004, 231(4), 535-548.
[http://dx.doi.org/10.1016/j.jtbi.2004.07.008] [PMID: 15488530]
[88]
Di Virgilio, F. The therapeutic potential of modifying inflammasomes and NOD-like receptors. Pharmacol. Rev., 2013, 65(3), 872-905.
[http://dx.doi.org/10.1124/pr.112.006171] [PMID: 23592611]
[89]
Ismail, N.; Basten, A.; Briscoe, H.; Bretscher, P.A. Increasing the foreignness of an antigen, by coupling a second and foreign antigen to it, increases the T helper type 2 component of the immune response to the first antigen. Immunology, 2005, 115(1), 34-41.
[http://dx.doi.org/10.1111/j.1365-2567.2005.02128.x] [PMID: 15819695]
[90]
Chruszcz, M.; Mikolajczak, K.; Mank, N.; Majorek, K.A.; Porebski, P.J.; Minor, W. Serum albumins-Unusual allergens. Biochim. Biophys. Acta, Gen. Subj., 2013, 1830(12), 5375-5381.
[http://dx.doi.org/10.1016/j.bbagen.2013.06.016] [PMID: 23811341]
[91]
Azman, S.; Sekar, M.; Bonam, S.R.; Gan, S.H.; Wahidin, S.; Lum, P.T.; Dhadde, S.B. Traditional medicinal plants conferring protection against ovalbumin-induced asthma in experimental animals: A review. J. Asthma Allergy, 2021, 14, 641-662.
[http://dx.doi.org/10.2147/JAA.S296391] [PMID: 34163178]
[92]
Fuchs, B.; Braun, A. Improved mouse models of allergy and allergic asthma--chances beyond ovalbumin. Curr. Drug Targets, 2008, 9(6), 495-502.
[http://dx.doi.org/10.2174/138945008784533589] [PMID: 18537588]
[93]
Basto, A.P.; Badenes, M.; Almeida, S.C.P.; Martins, C.; Duarte, A.; Santos, D.M.; Leitão, A. Immune response profile elicited by the model antigen ovalbumin expressed in fusion with the bacterial OprI lipoprotein. Mol. Immunol., 2015, 64(1), 36-45.
[http://dx.doi.org/10.1016/j.molimm.2014.10.020] [PMID: 25467796]
[94]
Hargrave, K.E.; MacLeod, M.K.L.; Worrell, J.C. Antigen presenting cells: Professionals, amateurs, and spectators in the ‘long game’ of lung immunity. Int. J. Biochem. Cell Biol., 2022, 153, 106331.
[http://dx.doi.org/10.1016/j.biocel.2022.106331] [PMID: 36368596]
[95]
Schuijs, M.J.; Hammad, H.; Lambrecht, B.N. Professional and ‘amateur’ antigen-presenting cells in type 2 immunity. Trends Immunol., 2019, 40(1), 22-34.
[http://dx.doi.org/10.1016/j.it.2018.11.001] [PMID: 30502024]
[96]
Snapper, C.M. Distinct immunologic properties of soluble versus particulate antigens. Front. Immunol., 2018, 9, 598.
[http://dx.doi.org/10.3389/fimmu.2018.00598] [PMID: 29619034]
[97]
Catron, D.M.; Itano, A.A.; Pape, K.A.; Mueller, D.L.; Jenkins, M.K. Visualizing the first 50 hr of the primary immune response to a soluble antigen. Immunity, 2004, 21(3), 341-347.
[http://dx.doi.org/10.1016/j.immuni.2004.08.007] [PMID: 15357945]
[98]
Carrasco, Y.R. In vivo tracking of particulate antigen localization and recognition by B lymphocytes at lymph nodes. Methods Mol. Biol., 2018, 1707, 163-169.
[http://dx.doi.org/10.1007/978-1-4939-7474-0_11] [PMID: 29388106]
[99]
Kuroda, Y. Biophysical studies of amorphous protein aggregation and in vivo immunogenicity. Biophys. Rev., 2022, 14(6), 1495-1501.
[http://dx.doi.org/10.1007/s12551-022-01011-y] [PMID: 36465085]
[100]
Ratanji, K.D.; Derrick, J.P.; Dearman, R.J.; Kimber, I. Immunogenicity of therapeutic proteins: Influence of aggregation. J. Immunotoxicol., 2014, 11(2), 99-109.
[http://dx.doi.org/10.3109/1547691X.2013.821564] [PMID: 23919460]
[101]
Wang, W.; Singh, S.K.; Li, N.; Toler, M.R.; King, K.R.; Nema, S. Immunogenicity of protein aggregates-Concerns and realities. Int. J. Pharm., 2012, 431(1-2), 1-11.
[http://dx.doi.org/10.1016/j.ijpharm.2012.04.040] [PMID: 22546296]
[102]
Savina, A.; Amigorena, S. Phagocytosis and antigen presentation in dendritic cells. Immunol. Rev., 2007, 219(1), 143-156.
[http://dx.doi.org/10.1111/j.1600-065X.2007.00552.x] [PMID: 17850487]
[103]
Canton, J. Macropinocytosis: New insights into its underappreciated role in innate immune cell surveillance. Front. Immunol., 2018, 9, 2286.
[http://dx.doi.org/10.3389/fimmu.2018.02286] [PMID: 30333835]
[104]
Lim, J.P.; Gleeson, P.A. Macropinocytosis: An endocytic pathway for internalising large gulps. Immunol. Cell Biol., 2011, 89(8), 836-843.
[http://dx.doi.org/10.1038/icb.2011.20] [PMID: 21423264]
[105]
Ols, S.; Yang, L.; Thompson, E.A.; Pushparaj, P.; Tran, K.; Liang, F.; Lin, A.; Eriksson, B.; Karlsson, H.G.B.; Wyatt, R.T.; Loré, K. Route of vaccine administration alters antigen trafficking but not innate or adaptive immunity. Cell Rep., 2020, 30(12), 3964-3971.e7.
[http://dx.doi.org/10.1016/j.celrep.2020.02.111] [PMID: 32209459]
[106]
Sei, J.J.; Haskett, S.; Kaminsky, L.W.; Lin, E.; Truckenmiller, M.E.; Bellone, C.J.; Buller, R.M.; Norbury, C.C. Peptide-MHC-I from endogenous antigen outnumber those from exogenous antigen, irrespective of APC phenotype or activation. PLoS Pathog., 2015, 11(6), e1004941.
[http://dx.doi.org/10.1371/journal.ppat.1004941] [PMID: 26107264]
[107]
Baker, M.; Reynolds, H.M.; Lumicisi, B.; Bryson, C.J. Immunogenicity of protein therapeutics: The key causes, consequences and challenges. Self Nonself, 2010, 1(4), 314-322.
[http://dx.doi.org/10.4161/self.1.4.13904] [PMID: 21487506]
[108]
Alberts, B.; Johnson, A.; Lewis, J. Proteins. In: Molecular Biology of the Cell, 4th ed.; Garland Science: New York, 2002.
[109]
Squire, J.M.; Parry, D.A.D. Fibrous protein structures: Hierarchy, history and heroes. Subcell. Biochem., 2017, 82, 1-33.
[http://dx.doi.org/10.1007/978-3-319-49674-0_1] [PMID: 28101857]
[110]
Khechinashvili, N.N.; Kondratyev, M.S.; Polozov, R.V. Thermodynamics of globular protein native structure. J. Biomol. Struct. Dyn., 2022, 1-4
[http://dx.doi.org/10.1080/07391102.2022.2046637] [PMID: 35345984]
[111]
Marsh, J.A.; Teichmann, S.A. Structure, dynamics, assembly, and evolution of protein complexes. Annu. Rev. Biochem., 2015, 84(1), 551-575.
[http://dx.doi.org/10.1146/annurev-biochem-060614-034142] [PMID: 25494300]
[112]
Erickson, H.P. Size and shape of protein molecules at the nanometer level determined by sedimentation, gel filtration, and electron microscopy. Biol. Proced. Online, 2009, 11(1), 32-51.
[http://dx.doi.org/10.1007/s12575-009-9008-x] [PMID: 19495910]
[113]
Lundahl, M.L.E.; Fogli, S.; Colavita, P.E.; Scanlan, E.M. Aggregation of protein therapeutics enhances their immunogenicity: Causes and mitigation strategies. RSC Chem. Biol., 2021, 2(4), 1004-1020.
[http://dx.doi.org/10.1039/D1CB00067E] [PMID: 34458822]
[114]
Howe, J.G.; Stack, G. Structural and functional impacts of amino acid substitutions that create blood group antigens: Implications for immunogenicity. Transfusion, 2017, 57(3), 541-553.
[http://dx.doi.org/10.1111/trf.13966] [PMID: 28164302]
[115]
Lemke, H. Immune response regulation by antigen receptors’ clone-specific nonself parts. Front. Immunol., 2018, 9, 1471.
[http://dx.doi.org/10.3389/fimmu.2018.01471] [PMID: 30034389]
[116]
Labrijn, A.F.; Janmaat, M.L.; Reichert, J.M.; Parren, P.W.H.I. Bispecific antibodies: A mechanistic review of the pipeline. Nat. Rev. Drug Discov., 2019, 18(8), 585-608.
[http://dx.doi.org/10.1038/s41573-019-0028-1] [PMID: 31175342]
[117]
Thorlaksen, C.; Schultz, H.S.; Gammelgaard, S.K.; Jiskoot, W.; Hatzakis, N.S.; Nielsen, F.S.; Solberg, H.; Foderà, V.; Bartholdy, C.; Groenning, M. In vitro and in vivo immunogenicity assessment of protein aggregate characteristics. Int. J. Pharm., 2023, 631, 122490.
[http://dx.doi.org/10.1016/j.ijpharm.2022.122490] [PMID: 36521637]
[118]
Center, R.J.; Boo, I.; Phu, L.; McGregor, J.; Poumbourios, P.; Drummer, H.E. Enhancing the antigenicity and immunogenicity of monomeric forms of hepatitis C virus E2 for use as a preventive vaccine. J. Biol. Chem., 2020, 295(21), 7179-7192.
[http://dx.doi.org/10.1074/jbc.RA120.013015] [PMID: 32299914]
[119]
Skolnick, J.; Gao, M. The role of local versus nonlocal physicochemical restraints in determining protein native structure. Curr. Opin. Struct. Biol., 2021, 68, 1-8.
[http://dx.doi.org/10.1016/j.sbi.2020.10.008] [PMID: 33129066]
[120]
Mishra, P.; Jha, S.K. The native state conformational heterogeneity in the energy landscape of protein folding. Biophys. Chem., 2022, 283, 106761.
[http://dx.doi.org/10.1016/j.bpc.2022.106761] [PMID: 35101819]
[121]
Scheiblhofer, S.; Laimer, J.; Machado, Y.; Weiss, R.; Thalhamer, J. Influence of protein fold stability on immunogenicity and its implications for vaccine design. Expert Rev. Vaccines, 2017, 16(5), 479-489.
[http://dx.doi.org/10.1080/14760584.2017.1306441] [PMID: 28290225]
[122]
Harper, M.; Lema, F.; Boulot, G.; Poljak, R.J. Antigen specificity and cross-reactivity of monoclonal anti-lysozyme antibodies. Mol. Immunol., 1987, 24(2), 97-108.
[http://dx.doi.org/10.1016/0161-5890(87)90081-2] [PMID: 2441250]
[123]
Mohan, S.; Sinha, N.; Smith-Gill, S.J. Modeling the binding sites of anti-hen egg white lysozyme antibodies HyHEL-8 and HyHEL-26: An insight into the molecular basis of antibody cross-reactivity and specificity. Biophys. J., 2003, 85(5), 3221-3236.
[http://dx.doi.org/10.1016/S0006-3495(03)74740-7] [PMID: 14581222]
[124]
Koch, C.; Jensen, S.S.; Øster, A.; Houen, G. A comparison of the immunogenicity of the native and denatured forms of a protein. Acta Pathol. Microbiol. Scand. Suppl., 1996, 104(1-6), 115-125.
[http://dx.doi.org/10.1111/j.1699-0463.1996.tb00696.x] [PMID: 8619913]
[125]
Lemoine, C.; Thakur, A.; Krajišnik, D.; Guyon, R.; Longet, S.; Razim, A.; Górska, S.; Pantelic, I.; Ilic, T.; Nikolic, I.; Lavelle, E.C.; Gamian, A.; Savic, S. Technological approaches for improving vaccination compliance and coverage. Vaccines, 2020, 8(2), 304.
[http://dx.doi.org/10.3390/vaccines8020304]
[126]
Zhang, L.; Wang, W.; Wang, S. Effect of vaccine administration modality on immunogenicity and efficacy. Expert Rev. Vaccines, 2015, 14(11), 1509-1523.
[http://dx.doi.org/10.1586/14760584.2015.1081067] [PMID: 26313239]
[127]
Wallis, J.; Shenton, D.P.; Carlisle, R.C. Novel approaches for the design, delivery and administration of vaccine technologies. Clin. Exp. Immunol., 2019, 196(2), 189-204.
[http://dx.doi.org/10.1111/cei.13287] [PMID: 30963549]
[128]
Maira-Litrán, T. Immunization of mice. Curr. Protoc. Mol. Biol., 2017, 117, 11.4.1-11.4.11.
[http://dx.doi.org/10.1002/cpmb.30]
[129]
Vaccine Administration Route and Site I CDC. Available from: https://www.cdc.gov/vaccines/hcp/admin/administer-vaccines.html (Revised February 22nd, 2023)
[130]
Park, J.H.; Lee, H.K. Delivery routes for COVID-19 vaccines. Vaccines, 2021, 9(5), 524.
[http://dx.doi.org/10.3390/vaccines9050524] [PMID: 34069359]
[131]
Menon, I.; Bagwe, P.; Gomes, K.B.; Bajaj, L.; Gala, R.; Uddin, M.N.; D’Souza, M.J.; Zughaier, S.M. Microneedles: A new generation vaccine delivery system. Micromachines, 2021, 12(4), 435.
[http://dx.doi.org/10.3390/mi12040435] [PMID: 33919925]
[132]
Schellekens, H. Immunogenicity of therapeutic proteins. Nephrol. Dial. Transplant., 2003, 18(7), 1257-1259.
[http://dx.doi.org/10.1093/ndt/gfg164] [PMID: 12808158]
[133]
Hughes, S.M.; Amadi, B.; Mwiya, M.; Nkamba, H.; Tomkins, A.; Goldblatt, D. Dendritic cell anergy results from endotoxemia in severe malnutrition. J. Immunol., 2009, 183(4), 2818-2826.
[http://dx.doi.org/10.4049/jimmunol.0803518] [PMID: 19625645]
[134]
Faulkner, L.; Meng, X.; Park, B.K.; Naisbitt, D.J. The importance of hapten-protein complex formation in the development of drug allergy. Curr. Opin. Allergy Clin. Immunol., 2014, 14(4), 293-300.
[http://dx.doi.org/10.1097/ACI.0000000000000078] [PMID: 24936850]
[135]
Adamo, R.; Nilo, A.; Castagner, B.; Boutureira, O.; Berti, F.; Bernardes, G.J.L. Synthetically defined glycoprotein vaccines: Current status and future directions. Chem. Sci., 2013, 4(8), 2995-3008.
[http://dx.doi.org/10.1039/c3sc50862e] [PMID: 25893089]
[136]
Hamley, I.W. Lipopeptides for vaccine development. Bioconjug. Chem., 2021, 32(8), 1472-1490.
[http://dx.doi.org/10.1021/acs.bioconjchem.1c00258] [PMID: 34228433]
[137]
Cocinero, E.J.P. Carbohydrates. Top. Curr. Chem., 2015, 364, 299-333.
[http://dx.doi.org/10.1007/128_2014_596] [PMID: 25667011]
[138]
Reyna-Margarita, H.R.; Irais, C.M.; Mario-Alberto, R.G.; Agustina, R.M.; Luis-Benjamín, S.G.; David, P.E. Plant phenolics and lectins as vaccine adjuvants. Curr. Pharm. Biotechnol., 2019, 20(15), 1236-1243.
[http://dx.doi.org/10.2174/1389201020666190716110705] [PMID: 31333121]
[139]
He, S.; Simpson, B.K.; Sun, H.; Ngadi, M.O.; Ma, Y.; Huang, T. Phaseolus vulgaris lectins: A systematic review of characteristics and health implications. Crit. Rev. Food Sci. Nutr., 2018, 58(1), 70-83.
[http://dx.doi.org/10.1080/10408398.2015.1096234] [PMID: 26479307]

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