Role of Ia antigens in graft vs. host reactions. II. Molecular and functional analysis of T cell alloreactivity by the characterization of host Ia antigens on alloactivated donor T cells.
Graft vs. host response (GVHR)-activated donor T cells bind to stimulatory host cell-derived Ia antigens. Radioimmune cell-binding assays demonstrate that activated donor T cells acquire both host I-A and I-E alloantigens on their surface. Approximately threefold to fivefold less I-E products than I-A products are transferred. Immunoprecipitation and one-dimensional and two-dimensional gel electrophoresis analyses show that radioiodinated alpha and beta polypeptide chains of both I-A and I-E-encoded host Ia molecules may be transferred in an apparently structurally unaltered form from host cells to donor cells. Biosynthetic studies indicate that [35S]methionine-labeled activated donor T cells do not synthesize Ia antigens of the donor haplotype. Functional analyses with fluorescence-activated cell sorter sorted donor T cell subpopulations show that donor T cells that bind host I-A antigens preferentially cooperate with nonimmune host B cells. Donor T cells that do not bind detectable amounts of host I-A antigens preferentially help nonimmune donor B cells. By contrast, donor T cells that either bind or do not bind host I-A antigens display no H-2-restricted interaction and help both donor and host immune B cells. These data reveal that the Ia antigen-binding specificity of distinct functional subpopulations of alloactivated donor T cells regulates their I-region-restricted (self or allo) helper activity for nonimmune B cells but not immune B cells. Furthermore, they suggest that T cell-macrophage and T cell-B cell collaboration is mediated by a complementary anti-Ia:Ia receptor:ligand type of interaction in which the receptor of a T cell binds to the ligand of an antigen-presenting macrophage and/or B cell.
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D000954:Antigens, Surface; D001665:Binding Sites; D011232:Chemical Precipitation; D005455:Fluorescent Antibody Technique; D006087:Graft vs Host Reaction; D006462:Hemolytic Plaque Technique; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D046911:Macromolecular Substances; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D010641:Phenotype; D011817:Rabbits; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances