A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections and cancer cells. However, information on TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8+ TCR repertoires for two dominant viral epitopes: pp65495503 (NLV) of cytomegalovirus and M15866 (GIL) of influenza A virus. The highly individualized repertoires (875,533 or clonotypes per subject) comprised thousands of unique TCR and TCR sequences and dozens of distinct CDR3 and CDR3 motifs. However, diversity is effectively restricted by preferential V-J combinations, CDR3 lengths, and CDR3/CDR3 pairings. To investigate the structural underpinnings of this remarkable diversity, we determined the crystal structures of three GIL-specific TCRs bound to GILHLA-A2 to as low as 1.7 resolution. Our results show that there are multiple structurally distinct solutions to recognizing an identical peptide-MHC ligand with sufficient affinity and provide a potential explanation for the lower diversity of GIL-specific than NLV-specific repertoires. These anti-viral TCRs occupied up to 3.4% of the CD8+ TCR repertoire, ensuring broad T cell responses to single epitopes. Our portrait of two anti-viral TCR repertoires may inform development of predictors of immune protection.
| Yang, Xinbo; Chen, Guobing; Weng, Nan-Ping et al. (2017) Structural basis for clonal diversity of the human T-cell response to a dominant influenza virus epitope. J Biol Chem 292:18618-18627 |
| Chen, Guobing; Yang, Xinbo; Ko, Annette et al. (2017) Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens. Cell Rep 19:569-583 |
