Peptide ligand-induced conformation and surface expression of the L^d class I MHC molecule

Abstract

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 (β²m) 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 ²m. 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.