EpiVax, Inc., Providence, RI, United States.
Center for Vaccines and Immunology, University of Georgia, Athens, GA, United States.
Front Immunol. 2023 Nov 24;14:1290688. doi: 10.3389/fimmu.2023.1290688. eCollection 2023.
Pathogens escape host defenses by T-cell epitope mutation or deletion (immune escape) and by simulating the appearance of human T cell epitopes (immune camouflage). We identified a highly conserved, human-like T cell epitope in non-structural protein 7 (NSP7) of SARS-CoV-2, RNA-dependent RNA polymerase (RdRp) hetero-tetramer complex. Remarkably, this T cell epitope has significant homology to a T regulatory cell epitope (Tregitope) previously identified in the Fc region of human immunoglobulin G (IgG) (Tregitope 289). We hypothesized that the SARS-CoV-2 NSP7 epitope (NSP7-289) may induce suppressive responses by engaging and activating pre-existing regulatory T cells. We therefore compared NSP7-289 and IgG Tregitopes (289 and 289z, a shorter version of 289 that isolates the shared NSP7 epitope) . Tregitope peptides 289, 289z and NSP7-289 bound to multiple HLA-DRB1 alleles and suppressed CD4+ and CD8+ T cell memory responses. Identification and validation of SARS-CoV-2 NSP7-289 provides further evidence of immune camouflage and suggests that pathogens can use human-like epitopes to evade immune response and potentially enhance host tolerance. Further exploration of the role of cross-conserved Tregs in human immune responses to pathogens such as SARS-CoV-2 is warranted.
病原体通过 T 细胞表位突变或缺失（免疫逃逸）以及模拟人类 T 细胞表位的外观（免疫伪装）来逃避宿主防御。我们在 SARS-CoV-2 的非结构蛋白 7（NSP7）、RNA 依赖性 RNA 聚合酶（RdRp）异源四聚体复合物中鉴定出一个高度保守的、类似人类的 T 细胞表位。值得注意的是，这个 T 细胞表位与先前在人免疫球蛋白 G（IgG）Fc 区域鉴定出的 T 调节细胞表位（Tregitope）具有显著的同源性（Tregitope 289）。我们假设，SARS-CoV-2 的 NSP7 表位（NSP7-289）可能通过与预先存在的调节性 T 细胞结合和激活来诱导抑制性反应。因此，我们比较了 NSP7-289 和 IgG Tregitope（289 和 289z，289 的较短版本，分离出共同的 NSP7 表位）。Tregitope 肽 289、289z 和 NSP7-289 与多个 HLA-DRB1 等位基因结合，并抑制 CD4+和 CD8+T 细胞记忆反应。SARS-CoV-2 NSP7-289 的鉴定和验证进一步证明了免疫伪装的存在，并表明病原体可以利用类似人类的表位来逃避免疫反应，并可能增强宿主的耐受性。进一步探索交叉保守的 Tregs 在人类对 SARS-CoV-2 等病原体免疫反应中的作用是必要的。
