Contribution of T cell receptor affinity to overall avidity for virus-specific CD8(+) T cell responses
AuthorKedzierska, K; La Gruta, NL; Davenport, MP; Turner, SJ; Doherty, PC
Source TitlePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
PublisherNATL ACAD SCIENCES
University of Melbourne Author/sKedzierska, Katherine; La Gruta, Nicole; Turner, Stephen; Doherty, Peter
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsKedzierska, K., La Gruta, N. L., Davenport, M. P., Turner, S. J. & Doherty, P. C. (2005). Contribution of T cell receptor affinity to overall avidity for virus-specific CD8(+) T cell responses. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 102 (32), pp.11432-11437. https://doi.org/10.1073/pnas.0504851102.
Access StatusAccess this item via the Open Access location
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1183580
C1 - Journal Articles Refereed
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.
KeywordsCellular Immunology; Immune System and Allergy
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