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

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TitleSequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8(+) TCR Repertoires to Immunodominant Viral Antigens.
Publication TypeJournal Article
Year of Publication2017
AuthorsChen, G, Yang, X, Ko, A, Sun, X, Gao, M, Zhang, Y, Shi, A, Mariuzza, RA, Weng, N-P
JournalCell Rep
Volume19
Issue3
Pagination569-583
Date Published2017 Apr 18
ISSN2211-1247
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 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.

DOI10.1016/j.celrep.2017.03.072
Alternate JournalCell Rep
PubMed ID28423320