TCR β-Chain Sharing in Human CD8+ T Cell Responses to Cytomegalovirus and EBV

被引:87
作者
Venturi, Vanessa [1 ]
Chin, Hui Yee [1 ]
Asher, Tedi E. [2 ]
Ladell, Kristin [3 ]
Scheinberg, Phillip [2 ]
Bornstein, Ethan [2 ]
van Bockel, David [4 ,5 ]
Kelleher, Anthony D. [4 ,5 ]
Douek, Daniel C. [2 ]
Price, David A. [2 ,3 ]
Davenport, Miles P. [1 ]
机构
[1] Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Kensington, NSW 2052, Australia
[2] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
[3] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales
[4] Univ New S Wales, St Vincents Hosp, Ctr Immunol, Sydney, NSW, Australia
[5] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia
基金
美国国家卫生研究院; 澳大利亚研究理事会; 英国医学研究理事会;
关键词
D O I
10.4049/jimmunol.181.11.7853
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The CD8(+) TCR repertoires specific for many immunogenic epitopes of CMV and EBV are dominated by a few TCR clonotypes and involve public TCRs that are shared between many MHC-matched individuals. In previous studies, we demonstrated that the observed sharing of epitope-specific TCR beta chains between individuals is strongly associated with TCR beta production frequency, and that a process of convergent recombination facilitates the more efficient production of some TCRP sequences. In this study, we analyzed a total of 2836 TCR beta sequences from 23 CMV-infected and 10 EBV-infected individuals to investigate the factors that influence the sharing of TCR beta sequences in the CD8(+) T cell responses to two immunodominant HLA-A*0201-restricted epitopes from these viruses. The most shared TCR beta amino acid sequences were found to have two features that indicate efficient TCR beta production, as follows: 1) they required fewer nucleotide additions, and 2) they were encoded by a greater variety of nucleotide sequences. We used simulations of random V(D)J recombination to demonstrate that the in silico TCR beta production frequency was predictive of the extent to which both TCR beta nucleotide and amino acid sequences were shared in vivo. These results suggest that TCR beta production frequency plays an important role in the interindividual sharing of TCR beta sequences within CD8(+) T cell responses specific for CMV and EBV. The Journal of Immunology, 2008, 181: 7853-7862.
引用
收藏
页码:7853 / 7862
页数:10
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