title: High prevalence of low affinity peptide-MHC II tetramer-negative effectors during polyclonal CD4+ T cell responses.
abstract: T cell affinity for antigen initiates adaptive immunity. However, the contribution of low affinity cells to a response is unknown as it has not been possible to assess the entire affinity range of a polyclonal T cell repertoire. In this study, we used a highly sensitive two-dimensional binding assay to identify low affinity cells in polyclonal autoreactive and pathogen-reactive CD4(+) T cell populations specific for myelin oligodendrocyte glycoprotein (MOG) and lymphocytic choriomeningitis virus (LCMV) antigens, respectively. Low affinity CD4(+) T cells, below detection with peptide-major histocompatibility complex class II tetramers, were at least as frequent as high affinity responders and contributed significant effector cytokines in both primary antigen-specific responses. We further demonstrated that MOG- and LCMV-specific CD4(+) T cells possessed similarly broad ranges in their affinities (>100-fold wide), only differing in the frequencies of low and high affinity cells. Thus, low as well as high affinity CD4(+) T cells are critical effectors in autoimmune and pathogen-specific responses.
authors.affiliation: Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Sabatino
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.forename: Brian D
authors.initials: BD
authors.lastname: Evavold
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000949:Histocompatibility Antigens Class II