title: Fixing an irrelevant TCR alpha chain reveals the importance of TCR beta diversity for optimal TCR alpha beta pairing and function of virus-specific CD8+ T cells.
abstract: TCR repertoire diversity can influence the efficacy of CD8(+) T-cell populations, with greater breadth eliciting better protection. We analyzed TCR beta diversity and functional capacity for influenza-specific CD8(+) T cells expressing a single TCR alpha chain. Mice (A7) transgenic for the H2K(b)OVA(257-264)-specific V alpha 2.7 TCR were challenged with influenza to determine how fixing this "irrelevant" TCR alpha affects the "public" and restricted D(b)NP(366) (+)CD8(+) versus the "private" and diverse D(b)PA(224) (+)CD8(+) responses. Though both D(b)NP(366) (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets are generated in virus-primed A7 mice, the constrained D(b)NP(366) (+)CD8(+) population lacked the characteristic, public TCRV beta 8.3, and consequently was reduced in magnitude and pMHC-I avidity. For the more diverse D(b)PA(224) (+)CD8(+) T cells, this particular forcing led to a narrowing and higher TCR beta conservation of the dominant V beta 7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCR beta diversity and the cytokine profiles were reduced for the D(b)NP(366) (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets in spleen, the latter measure of polyfunctionality was comparable for T cells recovered from the infected lungs of A7 and control mice. Even "sub-optimal" TCR alpha beta pairs can operate effectively when exposed in a milieu of high virus load. Thus, TCR beta diversity is important for optimal TCR alpha beta pairing and function when TCR alpha is limiting.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Vic 3010, Australia.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Valkenburg
authors.forename: E Bridie
authors.initials: EB
authors.lastname: Day
authors.forename: Natasha G
authors.initials: NG
authors.lastname: Swan
authors.forename: Hayley A
authors.initials: HA
authors.lastname: Croom
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D019674:Genes, T-Cell Receptor beta / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D055503:Protein Multimerization / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014758:Viral Core Proteins / Q000276:immunology
chemical_list: D016207:Cytokines; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014758:Viral Core Proteins; C102366:nucleoprotein (366-374), influenza virus; D010047:Ovalbumin