In vitro production of a hybrid monoclonal antibody that preferentially binds to cells that express both HLA-A2 and HLA-B7

A hybrid mouse monoclonal IgGl having one low affinity combining site for HLA-A2 and one low affinity combining site for HLA-B7 was made by the chemical method of Nisonoff and Palmer (Science 143:376,1964). This involved selective reduction of interchain disulphides, a splitting of the IgGl into half molecules at low pH and ionic strength, and reassociation of the half molecules by neutralization. Serologically active hybrids were separated from parental IgGl by an absorbtion procedure and recovered in about 10% yield. The hybrid discriminated between cells that express either HLA-A2 of HLA-B7 from cells that express both A2 and B7. This is because it could bind bivalently to the cell with both A2 and B7 but could only bind with a single combining site to cells expressing A2 or B7. The consequence of these different modes of attachment was to give up to sevenfold greater binding to the cell expressing A2 and B7 in comparison to the cell expressing only A2 or B7.