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


ABSTRACT: 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: pp65495-503 (NLV) of cytomegalovirus and M158-66 (GIL) of influenza A virus. The highly individualized repertoires (87-5,533 ? or ? clonotypes per subject) comprised thousands of unique TCR? and TCR? sequences and dozens of distinct complementary determining region (CDR)3? and CDR3? motifs. However, diversity is effectively restricted by preferential V-J combinations, CDR3 lengths, and CDR3?/CDR3? 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+ TCR? 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.

SUBMITTER: Chen G 

PROVIDER: S-EPMC5472051 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

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