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Cell Rep. 2017 Apr 18;19(3):569-583. doi: 10.1016/j.celrep.2017.03.072.

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

Author information

1
Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
2
W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
3
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
4
Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Electronic address: wengn@mail.nih.gov.

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.

KEYWORDS:

CD8 T cells; TCR repertoire; TCR-pMHC structure; human; αβ TCRs for CMV-NLV; αβ TCRs for IAV-GIL

PMID:
28423320
PMCID:
PMC5472051
DOI:
10.1016/j.celrep.2017.03.072
[Indexed for MEDLINE]
Free PMC Article

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