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：2004
卷号：101
期号：14
页码：4942-4947
DOI：10.1073/pnas.0401279101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The CD8+ T cell response to the immunodominant DbNP366 epitope has been analyzed sequentially to determine the prevalence and persistence of different T cell antigen receptor (TCR)V{beta}8.3 clonotypes after primary and secondary influenza virus challenge. Based on the length and amino acid sequences of the complementarity-determining region 3 of TCR{beta} (CDR3{beta}) loop and associated J{beta} usage, the same dominant TCR{beta} signatures were found in the blood, the spleen, and the site of virus-induced pathology in the infected respiratory tract. Longitudinal analysis demonstrated that TCR{beta} prominent in the antigen-driven phase of response persisted into memory and were again expanded after secondary challenge. A proportion of these high-frequency TCR{beta} expressed "public" CDR3{beta} sequences that were detected in every mouse sampled, whereas others were found more than once but were not invariably present. Analysis of N-region nucleotide diversity established that as many as 10 different nucleic acid sequences (maximum of four "nucleotypes" in any one mouse) could encode a single public TCR{beta} amino acid sequence. Conversely, whereas some of the unique, "private" TCR{beta} achieved a substantial clone size, they were always specified by a single nucleotype. Although there is a strong stochastic element in this response, the public TCR{beta} seem to represent a "best fit" for this immunodominant epitope, are selected preferentially from the naive TCR repertoire, and assume even greater prominence after secondary challenge.
关键词：CD8+ T cells ; T cell receptor repertoire ; influenza A virus
