HUMAN MONOCLONAL ANTIBODIES TO HLA-DR DETERMINANTS

THE IMMUNE RESPONSE IN MAN IS REGULATED BY ORDERED INTERACTIONS BETWEEN FUNCTIONALLY AND PHENOTYPICALLY DISTINCT LYMPHOID CELLS (T CELLS AND THEIR SUBSETS, B CELLS AND MONOCYTES) IN THE CONTEXT OF IA-LIKE MOLECULES ENCODED BY THE HLA COMPLEX OF GENES. THUS, THE PRODUCTS OF THESE GENES (E.G., DR, DS, SB) CONTROL THE PROLIFERATIVE RESPONSE OF T CELLS IN MIXED LYMPHOCYTE REACTIONS, ANTIGEN PRESENTATION TO T CELLS BY MACROPHAGES AND COLLABORATION BETWEEN T AND B CELLS. TEN ALLELES OF THE HLA-DR LOCUS HAVE BEEN IDENTIFIED AND, IN ADDITION TO INFLUENCING ALLOGRAFT SURVIVAL, ALLELES OF THIS LOCUS HAVE BEEN ASSOCIATED WITH SUSCEPTIBILITY TO A NUMBER OF DISEASES INCLUDING SYSTEMIC LUPUS (SLE), RHEUMATOID ARTHRITIS (RA), AND MULTIPLE SCLEROSIS. WE PROPOSE TO PRODUCE A PANEL OF HUMAN MONOCLONAL ANTI-DR (POLYMORPHIC) ALLOANTIBODIES. A HUMAN-MOUSE DERIVED MYELOMA LINE, SHOWN TO FUSE EFFICIENTLY TO HUMAN B CELLS AND PRODUCE STABLE HUMAN IMMUNOGLOBULIN-SECRETING HYBRIDOMAS, WILL BE FUSED TO B CELLS ISOLATED FROM NORMAL MULTIPAROUS WOMEN AND/OR TRANSFUSION RECIPIENTS KNOWN TO CONTAIN SPECIFIC ANTI-DR ANTIBODIES IN THEIR SERA. THE GENERATION OF THESE ANTIBODIES WILL ALLOW A GREATER UNDERSTANDING OF THEIR SPECIFICITY AND FUNCTIONAL EFFECTS ON IMMUNE FUNCTIONS OF NORMAL AND DISEASED INDIVIDUALS. ULTIMATELY, THESE ANTIBODIES MAY BE USEFUL IN THE DIAGNOSIS AND TREATMENT OF AUTOIMMUNE DISORDERS.