文章基本信息

标题：Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses
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作者：E. Bridie Day ; Carole Guillonneau ; Stephanie Gras 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：23
页码：9536-9541
DOI：10.1073/pnas.1106851108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Pathogen-specific responses are characterized by preferred profiles of peptide+class I MHC (pMHCI) glycoprotein-specific T-cell receptor (TCR) Variable (V)-region use. How TCRV-region bias impacts TCR{beta} heterodimer selection and resultant diversity is unclear. The DbPA224-specific TCR repertoire in influenza A virus-infected C57BL/6J (B6) mice exhibits a preferred TCRV-region bias toward the TRBV29 gene segment and an optimal complementarity determining region (CDR3) {beta}-length of 6 aa. Despite these restrictions, DbPA224-specific BV29+ T cells use a wide array of unique CDR3{beta} sequences. Structural characterization of a single, TRBV29+DbPA224-specific TCR{beta}-pMHCI complex demonstrated that CDR3 amino acid side chains made specific peptide interactions, but the CDR3{beta} main chain exclusively contacted peptides. Thus, length but not amino acid sequence was key for recognition and flexibility in V{beta}-region use. In support of this hypothesis, retrovirus expression of the DbPA224-specific TCRV-chain was used to constrain pairing within a naive/immune epitope-specific repertoire. The retrogenic TCRV paired with a diversity of CDR3{beta}s in the context of a preferred TCRV{beta} spectrum. Overall, these data provide an explanation for the combination of TCRV region bias and diversity within selected repertoires, even as they maintain exquisite pMHCI specificity.
关键词：T cell repertoire ; T-cell receptor bias ; crystal structure