PRODUCTION OF HLA MONOCLONAL ANTIBODIES BY B-CELL LINES

INFORMATION GENERATED IN THE PAST FEW YEARS HAS BEGUN TO ELUCIDATE THE GENETIC ORGANIZATION OF THE HLA COMPLEX AT A MOLECULAR LEVEL USING DNA AND PROTEIN BIOCHEMISTRY METHODS. THESE STUDIES INDICATE THAT MULTIPLE MOLECULES IN THE FORM OF HETERODIMERS ARE EXPRESSED ON THE CELL SURFACE AND THAT EACH HETERODIMER MAY CARRY SEVERAL EPITOPES. THESE EPITOPESARE, BY ANALOGY TO THE MOUSE, LIKELY TO BE INVOLVED IN CELL-CELL INTERACTIONS. LIKEWISE, THESE EPITOPES ARE LIKELY TO BE INVOLVED IN SUSCEPTIBILITY TO DISEASE AND IMPORTANT IN MATCHING FOR TRANSPLANTATION. CHARACTERIZATIONOF PATIENTS BY PROTEIN AND BY DNA METHODS IS NOT PRACTICAL. METHODS ARE TIME CONSUMING, EXPENSIVE, AND NOT ADAPTED TO USE IN HETEROZYGOTES. IDENTIFICATION OF MONOCLONAL ANTIBODIES AGAINST BIOLOGICALLYRELEVANT ISOTOPES WOULD HAVE SIGNIFICANT IMPACT. MOUSE ANTIHUMAN MONOCLONAL REAGENTS RECOGNIZE PRIMARILY MONOCLONALDETERMINANTS WITH ONLY A FEW RECOGNIZING POLYMORPHIC DETERMINANTS. HUMAN ANTIHUMAN MONOCLONAL ANTIBODIES OFFER THE ADVANTAGE OF EXQUISITE SPECIFICITY BUT ARE NOT STABLE. IN PHASE I, IT IS PROPOSED TO ESTABLISH HUMAN B-CELL LINES TRANSFORMED WITH EPSTEIN-BARR VIRUS THAT ARE PRODUCING ANTIBODY AGAINST EPITOPES ON HLA-D REGION MOLECULES AND TO DETERMINE THE FREQUENCY WITH WHICH REAGENTS THAT DEFINE NEW SUBTYPES ARE OBTAINED. THESE NEW SUBTYPES WILL BE CORRELATED WITH PUBLISHED STUDIES ON DNA POLYMORPHISM. THESE ANTIBODY-PRODUCING LINES ARE STABLE AND ESSENTIALLY MONOCLONAL IN NATURE.