Epitope mapping of the human surface suppressor/cytotoxic T cell molecule Tp32.
The complexity of the suppressor/cytotoxic subset marker of human T lymphocytes was demonstrated by biochemical analysis, cross-blocking experiments, phylogenetic comparisons, and functional studies. At the biochemical level, the antigen was shown to be a heteromultimer of at least three polypeptide chains covalently associated into four different higher m.w. species. Sixteen different murine monoclonal antibodies were used to map epitopes of this heteromultimeric complex. Cross-blocking experiments undertaken with six directly labeled reference antibodies identified at least seven spacially distinct epitopes. Flow microfluorometric analysis of peripheral blood lymphocytes showed two distinct subpopulations of bright and dull-stained cells that differed approximately 10-fold in antigen density. The distribution of epitopes on bright and dull cells was not uniform because in several combinations, blocking was observed on bright cells only. Studies with nonhuman primate T cells demonstrated a high degree of phylogenetic heterogeneity in the antigen. The combined cross-blocking and primate data divided the 17 antibodies into 15 groups. Each of the antibodies was capable of blocking lysis by alloreactive cytotoxic T lymphocytes, indicating that the mechanism of inhibition may not necessarily involve hindrance of an active site.
D000293:Adolescent; D000818:Animals; D000937:Antigen-Antibody Reactions; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D001029:Aotus trivirgatus; D001667:Binding, Competitive; D002428:Cebus; D011232:Chemical Precipitation; D002648:Child; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D006922:Hylobates; D008254:Macaca nemestrina; D002679:Pan troglodytes; D010215:Papio; D011148:Pongo pygmaeus; D012452:Saguinus; D012453:Saimiri; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000939:Epitopes