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

被引：107

作者：

Chen, Guobing ^{[1
]}

Yang, Xinbo ^{[2
,3
]}

Ko, Annette ^{[1
]}

Sun, Xiaoping ^{[1
]}

Gao, Mingming ^{[2
,3
]}

Zhang, Yongqing ^{[4
]}

Shi, Alvin ^{[1
]}

Mariuzza, Roy A. ^{[2
,3
]}

Weng, Nan-Ping ^{[1
]}

机构：

[1] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA

[2] Univ Maryland, WM Keck Lab Struct Biol, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA

[3] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA

[4] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA

来源：

CELL REPORTS | 2017年 / 19卷 / 03期

关键词：

T-CELL-RECEPTOR; CROSS-REACTIVITY; DRIVEN SELECTION; LYMPHOCYTE CTL; CLASS-II; CYTOMEGALOVIRUS; VIRUS; ALPHA; EXPANSION; AFFINITY;

D O I：

10.1016/j.celrep.2017.03.072

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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: pp65(495-503) (NLV) of cytomegalovirus and M1(58-66) (GIL) of influenza A virus. The highly individualized repertoires (87-5,533 alpha or beta clonotypes per subject) comprised thousands of unique TCRa and TCRb sequences and dozens of distinct complementary determining region (CDR) 3 alpha and CDR3 beta motifs. However, diversity is effectively restricted by preferential V-J combinations, CDR3 lengths, and CDR3a/ CDR3b 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(+) TCRb 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.

引用

页码：569 / 583

页数：15

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