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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.
Chen G1, Yang X2, Ko A1, Sun X1, Gao M2, Zhang Y3, Shi A1, Mariuzza RA2, Weng NP4.
Author information
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.
Copyright ? 2017. Published by Elsevier Inc.
KEYWORDS:
CD8 T cells; TCR repertoire; TCR-pMHC structure; human; αβ TCRs for CMV-NLV; αβ TCRs for IAV-GIL
PMID: 28423320 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.
Chen G1, Yang X2, Ko A1, Sun X1, Gao M2, Zhang Y3, Shi A1, Mariuzza RA2, Weng NP4.
Author information
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.
Copyright ? 2017. Published by Elsevier Inc.
KEYWORDS:
CD8 T cells; TCR repertoire; TCR-pMHC structure; human; αβ TCRs for CMV-NLV; αβ TCRs for IAV-GIL
PMID: 28423320 DOI: 10.1016/j.celrep.2017.03.072