Effective monitoring of evolving SARS-CoV-2 variants requires understanding the potential effect of mutations on immune evasion. Here, we predicted the impact of BA.2.86-associated mutations on SARS-CoV-2-specific T cell responses. First, evaluating the effect on known experimentally defined T cell epitopes, we found that 72% and 89% of the total SARS-CoV-2 CD4 and CD8 responses were 100% conserved, with lower rates (56% and 72%) for just spike, a major structural protein. Among the mutated spike epitopes, however, 96% and 62% still bound the same reported HLA-restricting alleles. Additional prediction analyses comparing the ancestral and BA.2 sequences with BA.2.86 mutations identified several potentially novel BA.2.86 epitopes. By simulating exposure with BA.2, the large number of epitopes conserved with BA.2.86 suggests that variant-specific epitopes induced following breakthrough infection or bivalent vaccination can bridge the gap between ancestral immunization and upcoming circulating variants, allowing for a more stable T cell response across viral evolution.

有效监测不断演变的 SARS-CoV-2 变体需要了解突变对免疫逃避的潜在影响。在这里，我们预测了 BA.2.86 相关突变对 SARS-CoV-2 特异性 T 细胞反应的影响。首先，评估对已知实验定义的 T 细胞表位的影响，我们发现 SARS-CoV-2 CD4 和 CD8 总反应中的 72% 和 89% 是 100% 保守的，仅刺突蛋白，一种主要的结构蛋白。然而，在突变的刺突表位中，96% 和 62% 仍然结合相同的报道的 HLA 限制性等位基因。将祖先序列和 BA.2 序列与 BA.2.86 突变进行比较的其他预测分析确定了几个潜在的新 BA.2.86 表位。通过模拟 BA.2 暴露，BA.2.86 保守的大量表位表明，突破性感染或二价疫苗接种后诱导的变体特异性表位可以弥合祖先免疫和即将到来的循环变体之间的差距，从而产生更稳定的 T 细胞病毒进化过程中的反应。