T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory T cells can effectively cross-recognize new SARS-CoV-2 variants with a broad array of mutations, such as the emergent hypermutated BA.2.86 variant. Here, we report in two separate cohorts, including healthy controls and individuals with chronic lymphocytic leukemia, that SARS-CoV-2 spike-specific CD4⁺ and CD8⁺ T cells induced by prior infection or vaccination demonstrate resilient immune recognition of BA.2.86. In both cohorts, we found largely preserved SARS-CoV-2 spike-specific CD4⁺ and CD8⁺ T cell magnitudes against mutated spike epitopes of BA.2.86. Functional analysis confirmed that both cytokine expression and proliferative capacity of SARS-CoV-2 spike-specific T cells to BA.2.86-mutated spike epitopes are similarly sustained. In summary, our findings indicate that memory CD4⁺ and CD8⁺ T cells continue to provide cell-mediated immune recognition to highly mutated emerging variants such as BA.2.86.

T 细胞对于介导严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 突破性感染的早期控制至关重要。然而，记忆 T 细胞是否能够有效地交叉识别具有广泛突变的新 SARS-CoV-2 变体（例如出现的超突变 BA.2.86 变体）仍不清楚。在这里，我们在两个单独的队列中报告，包括健康对照和慢性淋巴细胞白血病患者，先前感染或疫苗接种诱导的 SARS-CoV-2 刺突特异性 CD4 ⁺和 CD8 ⁺ T 细胞表现出对 BA.2.86 的弹性免疫识别。在这两个队列中，我们发现针对 BA.2.86 突变的刺突表位，很大程度上保留了 SARS-CoV-2 刺突特异性 CD4 ⁺和 CD8 ⁺ T 细胞数量。功能分析证实，SARS-CoV-2 刺突特异性 T 细胞对 BA.2.86 突变刺突表位的细胞因子表达和增殖能力同样持续。总之，我们的研究结果表明，记忆 CD4 ⁺和 CD8 ⁺ T 细胞继续为高度突变的新兴变体（例如 BA.2.86）提供细胞介导的免疫识别。