Functional and molecular analysis of three distinct HLA-DR4 beta-chains responsible for the MLR between HLA-Dw4, Dw15, and DKT2.
Differences in structure and function of HLA-class II molecules between HLA-DR4-related HLA-D specificities HLA-Dw4, Dw15, and DKT2 were investigated. Anti-HLA-DR framework monoclonal antibody HU-4 completely inhibited the one-way mixed lymphocyte reaction (MLR) between these specificities. HU-4 precipitated a monomorphic alpha-chain and a polymorphic beta-chain of human class II molecules from each B lymphoblastoid cell line (BLCL) homozygous for these three HLA-D specificities. We established IL 2-dependent T cell lines specific for streptococcal cell wall (SCW) antigen from peripheral blood lymphocytes (PBL) from four DR4-positive donors: an HLA-Dw4/DKT2 heterozygote, an HLA-Dw4/Dw12 heterozygote, an HLA-DKT2/D-blank heterozygote, and an HLA-Dw15/D-blank heterozygote. These T cell lines showed a proliferative response to SCW antigen in the presence of autologous or allogeneic antigen-presenting cells (APC) when T cell donors and APC donors shared at least one of the HLA-D specificities. This cooperation between the T cell line and APC was completely blocked by HU-4. We conclude from these data that the T cells could distinguish three distinct DR4 molecules expressed on APC of HLA-Dw4, Dw15, and DKT2 as restriction molecules at the presentation of SCW antigen.
D000911:Antibodies, Monoclonal / Q000032:analysis / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000276:immunology; D001667:Binding, Competitive; D002460:Cell Line; D000939:Epitopes / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008211:Lymphocyte Cooperation; D007959:Lymphocyte Culture Test, Mixed; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II