Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens

作者：Guobing Chen, Xinbo Yang, Annette Ko, Xiaoping Sun, Mingming Gao, Yongqing Zhang, Alvin Shi, Roy A. Mariuzza, Nan‐ping Weng · 发表于：Cell Reports · 年份：2017 · DOI：10.1016/j.celrep.2017.03.072 · 被引用次数：141 · 研究领域：Cytomegalovirus and herpesvirus research、Immunotherapy and Immune Responses、Virus-based gene therapy research

A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8 + TCR repertoires for two dominant viral epitopes: pp65 495–503 (NLV) of cytomegalovirus and M1 58–66 (GIL) of influenza A virus. The highly individualized repertoires (87–5,533 α or β clonotypes per subject) comprised thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary determining region (CDR)3α and CDR3β motifs. However, diversity is effectively restricted by preferential V-J combinations, CDR3 lengths, and CDR3α/CDR3β pairings. Structures of two GIL-specific TCRs bound to GIL–HLA-A2 provided a potential explanation for the lower diversity of GIL-specific versus NLV-specific repertoires. These anti-viral TCRs occupied up to 3.4% of the CD8 + TCRβ repertoire, ensuring broad T cell responses to single epitopes. Our portrait of two anti-viral TCR repertoires may inform the development of predictors of immune protection.