title: Low-affinity CD4+ T cells are major responders in the primary immune response.
abstract: A robust primary immune response has been correlated with the precursor number of antigen-specific T cells, as identified using peptide MHCII tetramers. However, these tetramers identify only the highest-affinity T cells. Here we show the entire CD4+ T-cell repertoire, inclusive of low-affinity T cells missed by tetramers, using a T-cell receptor (TCR) signalling reporter and micropipette assay to quantify naive precursors and expanded populations. In vivo limiting dilution assays reveal hundreds more precursor T cells than previously thought, with higher-affinity tetramer-positive T cells, comprising only 5-30% of the total antigen-specific naive repertoire. Lower-affinity T cells maintain their predominance as the primary immune response progresses, with no enhancement of survival of T cells with high-affinity TCRs. These findings demonstrate that affinity for antigen does not control CD4+ T-cell entry into the primary immune response, as a diverse range in affinity is maintained from precursor through peak of T-cell expansion.
authors.affiliation: Department of Microbiology and Immunology, Emory University, 1510 Clifton Rd NE, Atlanta Georgia, 30322, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Martinez
authors.affiliation: Department of Microbiology and Immunology, Emory University, 1510 Clifton Rd NE, Atlanta Georgia, 30322, USA.
authors.forename: Rakieb
authors.initials: R
authors.lastname: Andargachew
authors.affiliation: Department of Microbiology and Immunology, Emory University, 1510 Clifton Rd NE, Atlanta Georgia, 30322, USA.
authors.forename: Hunter A
authors.initials: HA
authors.lastname: Martinez
authors.affiliation: Department of Microbiology and Immunology, Emory University, 1510 Clifton Rd NE, Atlanta Georgia, 30322, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Evavold
mesh_terms: D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005620:Freund's Adjuvant; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics; D037342:Pertussis Toxin / Q000276:immunology; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013154:Spleen / Q000166:cytology; D015854:Up-Regulation
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D049452:Green Fluorescent Proteins; D005620:Freund's Adjuvant; D037342:Pertussis Toxin