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：2005
卷号：102
期号：32
页码：11432-11437
DOI：10.1073/pnas.0504851102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Prior analysis has characterized the clonal characteristics of effector CD8+ T cells specific for the prominent influenza A virus nucleoprotein (NP) and acid polymerase (PA) peptides presented by H2Db. Using a single-cell approach and determination of CDR3{beta} profiles, a limited, predominantly "public" repertoire was found for CD8+DbNP366+V{beta}8.3+ cells, whereas diverse and "private" T cell antigen receptor (TCR){beta} clonotypes were typical of the CD8+DbPA224+V{beta}7+ response. This single-cell approach has now been used to relate the contributions of particular clonotypes (or affinities) to high-avidity TCRs, as defined by binding under conditions of limiting tetramer availability. At least by the measure of CDR3{beta} usage, no difference could be found between total and high-avidity populations in the spectrum of TCR-pMHC affinities throughout the limited, and relatively public, CD8+DbNP366+V{beta}8.3+ populations. Conversely, the more even (by clone size), diverse, and private CD8+DbPA224+V{beta}7+ response was characterized by the clear partitioning of the largest T cell clones in the high-avidity compartment. These results suggest that the relatively constrained CD8+DbNP366+V{beta}8.3+ set utilizes a relatively narrow range of affinities, whereas the broader CD8+DbPA224+V{beta}7+ response is induced at a range of TCR-pMHC affinities. Thus, whereas TCR sequence (or affinity) appears to contribute substantially to the avidity profile of diverse virus-specific CD8+ populations, other mechanisms may be prominent where the TCR spectrum is more limited.
关键词：avidity ; influenza A virus ; T cell receptor repertoire ; TCR affinity
