title: Early establishment of diverse T cell receptor profiles for influenza-specific CD8(+)CD62L(hi) memory T cells.
abstract: Single-cell analysis of endogenous, primary CD8(+) T cell responses to the influenza D(b)NP(366) and D(b)PA(224) epitopes indicates that prominent clonotypes bearing "public" or "shared" T cell receptors (TCRs) subset early into CD62L(hi) and CD62L(lo) populations. The CD62L(lo) effectors divide more and are rapidly eliminated during the contraction phase, whereas stable CD62L(hi) memory populations persist in the long-term. Reflecting the high frequency of small CD62L(hi) clones expressing "private" TCRs, the TCR diversity range per mouse is generally two times higher within the CD62L(hi)CD8(+)D(b)NP(366)(+) set (1.6 times higher for CD62L(hi)CD8(+)D(b)PA(224)(+)) from 8 to >180 days after antigen challenge. Memory CD8(+)CD62L(hi) T cell precursors thus segregate from the outset into populations expressing "best-fit" and "suboptimal" TCR characteristics, with this pattern being maintained stably thereafter. Hence, our analysis suggests that early establishment of influenza-specific memory within the CD8(+)CD62L(hi) subset preserves clonal diversity and prevents "overdominance" by a few public, or shared, clones.
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: Vanessa
authors.initials: V
authors.lastname: Venturi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Field
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: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D005260:Female; D007156:Immunologic Memory / Q000502:physiology*; D009980:Influenza A virus; D019041:L-Selectin / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019041:L-Selectin