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Guobing Chen, Xinbo Yang, Annette Ko, Mingming Gao, Yongqing Zhang, Alvin Shi, Xiaoping Sun, Roy A Mariuzza, Nan-Ping Weng, Distinct features of human CD8 T cell TCR repertoire specific to influenza A virus matrix protein M1, The Journal of Immunology, Volume 196, Issue 1_Supplement, May 2016, Page 194.1, https://doi.org/10.4049/jimmunol.196.Supp.194.1
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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 lengths were different. Together, our findings revealed the size of the antigen-specific CD8 TCR repertoire, the consensus binding motifs in CDR3, binding affinity of TCR and pMHC, and shared patterns of TCR-pMHC interactions.
