Peptide ligand-induced conformation and surface expression of the Ld class I MHC molecule

NEWLY synthesized major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum are thought to bind peptides of foreign and endogenous antigens 1–4 . Several lines of evidence indicate that β-2 microglobulin (β 2 m) and/or peptide ligand participate in the intracellular transport and surface expression of class I molecules, but the nature of their involvement is still unclear 5,6 . Here we present evidence that culturing non-mutant cells (fibroblast, thymoma or mastocytoma) with a peptide ligand specific for the L d class I molecule of the mouse leads to a dramatic (fourfold) and specific induction of L d surface expression. Surprisingly, this peptide ligand-induced expression of L d does not result in an increased intracellular association of L d with β 2 m. These findings demonstrate that the previously reported decrease in surface expression of L d results from its failure to be saturated with endogenous self-peptide ligands. This unique feature of L d could also contribute to the fact that several virus-specific cytotoxic ? cell responses have been found to be L d -restricted.