THE SPECIFIC BINDING OF PEPTIDE LIGAND TO LD CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES DETERMINES THEIR ANTIGENIC STRUCTURE

To better understand the biological implications of the association of ligand with major histocompatibility complex class I molecules, we have studied the L(d) molecule of the mouse. The culturing of various nonselected cell lines with three different known L(d) peptide ligands resulted in a two- to fourfold specific increase in surface L(d) expression as detected by 10 of 11 different monoclonal antibodies (mAbs) recognizing L(d) epitopes. These findings suggest that L(d) molecules are not saturated with endogenous peptide ligands and thus have accessible binding sites. Exploiting this feature of L(d) we demonstrate that the physical association of L(d) with ligand is exquisitely specific, indicating that they function in determinant selection. In addition, a non-peptide-bound antigenic variant of L(d) was specifically detected with an exceptional mAb designated 64-3-7. In comparison with other L(d) molecules, 64-3-7+ L(d) molecules are not peptide ligand inducible, are more susceptible to proteolysis, lack beta-2 microglobulin association, and display a slower rate of oligosaccharide maturation. In spite of their deficiencies, the non-ligand-associated 64-3-7 L(d) molecules were detected on the surface of all cell type tested; however, they appear not to be recognized by alloreactive cytotoxic T lyphocytes.