Distinct features of human CD8 T cell TCR repertoire specific to influenza A virus matrix protein M1

作者：Guobing Chen, Xinbo Yang, Annette Ko, Mingming Gao, Yongqing Zhang, Alvin Shi, Xiaoping Sun, Roy A. Mariuzza, Nan‐ping Weng · 发表于：The Journal of Immunology · 年份：2016 · DOI：10.4049/jimmunol.196.supp.194.1 · 被引用次数：1 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、CAR-T cell therapy research

Abstract CD8 T cells play a vital role in the immune response to viral infection. Diversity of the T cell antigen receptor (TCR) is believed to be essential for the host to survive in this microorganism-rich world. However, there is limited information regarding the characteristics of the TCR repertoire to defined viral antigens in humans. Here, we report a comprehensive analysis of CD8 TCR repertoire diversity (size, V and J gene usage), the consensus binding motifs in CDR3, affinity, and structure of selected a/b paired TCRs to influenza A virus matrix protein M1 (GILGFVFTL, GIL) on HLA-A2+ healthy individuals. Using high-throughput sequencing coupled with the unique molecular identifier (UMI) method, we identified several hundred GIL-binding TCRa and TCRb. TRAV13-1 (63.2%) and TRAJ42 (72.5%) were most frequently found in alpha chain whereas TRBV19 (94.9%) and TRBJ2-5 (54.8%) were frequently found in beta chain. Furthermore, the length of the CDR3 amino acid region was highly restricted with over 70% of alpha (10) and of beta (11). CDR3 sequence analysis revealed shared motifs among different TCRs (a and b chains). We isolated paired expressed TCRa/b from single cells for further structural analysis. The affinity between TCRs and GIL-HLA-A2 complexes showed a wide range (1.8–191 mM). Finally, we resolved two crystal structures of TCRs-GIL-HLA-A2 complexes and found that the TCRs exhibited similar patterns of interactions with the antigen, even though the V, J, and CDR3 leng...