title: Contribution of T cell receptor affinity to overall avidity for virus-specific CD8+ T cell responses.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Melbourne, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D000939:Epitopes / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D000939:Epitopes; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D014758:Viral Core Proteins