HLA-DR epitope region definition by use of monoclonal antibody probes

Abstract

Definition of HLA-DR epitopes has been attempted by utilizing monoclonal antibody probes. Hybridoma antibodies L203 and L227, known to bind different epitopes on human Ia-like molecules, were tested for their ability to block cytotoxicity of monoclonal and allogeneic anti-DR antibodies. Monoclonal cytotoxic antibodies segregated into two groups: those more effectively blocked by L203, and those more effectively blocked by L227. Alloantisera also segregated into two groups, but according to their DR specificity. Anti-DR1, -2, and -3 alloantisera were effectively blocked by both L203 and L227, whereas anti-DR7, -w9, -w10, and MT1 alloantisera were not blocked by either. Blocking was not correlated with immunoglobulin class of the alloantibody and further definition of the mechanism of cytotoxicity blocking remains to be elucidated. Based on these data and prior binding and immunochemical studies with L203 and L227, a model is proposed in which the tertiary structure of each DR molecule, or complex of associated molecules on the cell surface, has two reference epitopes, one defined by L203, and another defined by L227. HLA-DR epitopes defined by the cytotoxic monoclonal or alloantibodies to the L203 or L227 epitope in order to begin epitope mapping or grouping.