Beijing Institute of Biotechnology, Beijing 100071, China.
Viruses. 2023 Mar 16;15(3):763. doi: 10.3390/v15030763.
T-cell immunity plays an important role in the control of SARS-CoV-2 and has a great cross-protective effect on the variants. The Omicron BA.1 variant contains more than 30 mutations in the spike and severely evades humoral immunity. To understand how Omicron BA.1 spike mutations affect cellular immunity, the T-cell epitopes of SARS-CoV-2 wild-type and Omicron BA.1 spike in BALB/c (H-2) and C57BL/6 mice (H-2) were mapped through IFNγ ELISpot and intracellular cytokine staining assays. The epitopes were identified and verified in splenocytes from mice vaccinated with the adenovirus type 5 vector encoding the homologous spike, and the positive peptides involved in spike mutations were tested against wide-type and Omicron BA.1 vaccines. A total of eleven T-cell epitopes of wild-type and Omicron BA.1 spike were identified in BALB/c mice, and nine were identified in C57BL/6 mice, only two of which were CD4 T-cell epitopes and most of which were CD8 T-cell epitopes. The A67V and Del 69-70 mutations in Omicron BA.1 spike abolished one epitope in wild-type spike, and the T478K, E484A, Q493R, G496S and H655Y mutations resulted in three new epitopes in Omicron BA.1 spike, while the Y505H mutation did not affect the epitope. These data describe the difference of T-cell epitopes in SARS-CoV-2 wild-type and Omicron BA.1 spike in H-2 and H-2 mice, providing a better understanding of the effects of Omicron BA.1 spike mutations on cellular immunity.
T 细胞免疫在控制 SARS-CoV-2 中发挥着重要作用，对变异株具有很强的交叉保护作用。Omicron BA.1 变体在刺突蛋白中包含 30 多个突变，严重逃避了体液免疫。为了了解 Omicron BA.1 刺突突变如何影响细胞免疫，通过 IFNγ ELISpot 和细胞内细胞因子染色测定，在 BALB/c（H-2）和 C57BL/6 小鼠（H-2）中对 SARS-CoV-2 野生型和 Omicron BA.1 刺突的 T 细胞表位进行了定位。在腺病毒 5 型载体编码同源刺突的疫苗接种小鼠的脾细胞中鉴定和验证了这些表位，并针对野生型和 Omicron BA.1 疫苗测试了涉及刺突突变的阳性肽。在 BALB/c 小鼠中鉴定到野生型和 Omicron BA.1 刺突的 11 个 T 细胞表位，在 C57BL/6 小鼠中鉴定到 9 个 T 细胞表位，其中只有 2 个是 CD4 T 细胞表位，大部分是 CD8 T 细胞表位。Omicron BA.1 刺突中的 A67V 和 Del 69-70 突变使野生型刺突中的一个表位失活，而 T478K、E484A、Q493R、G496S 和 H655Y 突变导致 Omicron BA.1 刺突中出现 3 个新表位，而 Y505H 突变不影响表位。这些数据描述了 SARS-CoV-2 野生型和 Omicron BA.1 刺突在 H-2 和 H-2 小鼠中的 T 细胞表位差异，为更好地了解 Omicron BA.1 刺突突变对细胞免疫的影响提供了依据。
