Monomorphic anti-HLA-A,B,C monoclonal antibodies detecting molecular subunits and combinatorial determinants.
Thirteen monoclonal antibodies that react with monomorphic determinants on the HLA-A,B,C-beta 2-microglobulin (beta 2m) molecule were characterized. Analysis of antibody activity included inhibition by papain-solubilized HLA antigens and free beta 2m, antibody binding to mouse-human somatic cell hybrids containing human chromosome 6 or 15, and antibody cross-reactivity with lymphocytes from nonhuman species. Two criteria for monomorphism were established: 1) equal inhibition or absorption of antibody activity by all papain-solubilized HLA antigens or cell lines of different HLA specificities tested; and 2) nonpolymorphic cross-reactivity within another species or subspecies. On the basis of soluble antigen inhibition and binding to somatic cell hybrids, 3 classes of antibodies were detected: anti-beta 2m, anti-heavy chain, and anti-complex (against a combinatorial determinant formed by heavy chain and beta 2m). Antibody cross-reaction patterns in nonhuman species were suggestive that these monomorphic antibodies detect a limited number of determinants, minimally one on each chain and 2 combinatorial determinants. Examination of the known primary sequences for HLA-A2, HLA-B7, H-2Kb, and mouse, rabbit and human beta 2m provides a molecular explanation for this limited mouse anti-HLA monomorphic antibody activity.
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002417:Cattle; D003429:Cross Reactions; D000939:Epitopes; D006071:Gorilla gorilla; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D006922:Hylobates; D008142:Lorisidae; D046911:Macromolecular Substances; D051379:Mice; D008815:Mice, Inbred Strains; D002679:Pan troglodytes; D010206:Papain / Q000494:pharmacology; D010215:Papio; D012453:Saimiri; D014418:Tupaiidae; D001613:beta 2-Microglobulin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006680:HLA Antigens; D046911:Macromolecular Substances; D001613:beta 2-Microglobulin; D010206:Papain