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 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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Chen G,Yang X,Ko A,Sun X,Gao M,Zhang Y,Shi A,Mariuzza RA,Weng NP

doi

10.1016/j.celrep.2017.03.072

subject

Has Abstract

pub_date

2017-04-18 00:00:00

pages

569-583

issue

3

issn

2211-1247

pii

S2211-1247(17)30449-7

journal_volume

19

pub_type

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