TY - JOUR AU - Kedzierska, K AU - La Gruta, NL AU - Davenport, MP AU - Turner, SJ AU - Doherty, PC Y2 - 2014/05/21 Y1 - 2005/08/09 SN - 0027-8424 UR - http://hdl.handle.net/11343/26430 AB - 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 H2D(b). Using a single-cell approach and determination of CDR3beta profiles, a limited, predominantly "public" repertoire was found for CD8(+)D(b)NP(366)(+)Vbeta8.3+ cells, whereas diverse and "private" T cell antigen receptor (TCR)beta clonotypes were typical of the CD8(+)D(b)PA(224)(+)Vbeta7+ 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 CDR3beta 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(+)D(b)NP(366)(+)Vbeta8.3+ populations. Conversely, the more even (by clone size), diverse, and private CD8(+)D(b)PA(224)(+)Vbeta7+ 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(+)D(b)NP(366)(+)Vbeta8.3+ set utilizes a relatively narrow range of affinities, whereas the broader CD8(+)D(b)PA(224)(+)Vbeta7+ 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. N1 - application/pdf LA - English PB - NATL ACAD SCIENCES KW - Cellular Immunology; Immune System and Allergy T1 - Contribution of T cell receptor affinity to overall avidity for virus-specific CD8(+) T cell responses DO - 10.1073/pnas.0504851102 IS - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA VL - 102 IS - 32 SP - 11432-11437 L1 - /bitstream/handle/11343/26430/116226_5275.pdf?sequence=1&isAllowed=n ER -