EXOGENOUS PEPTIDE LIGAND INFLUENCES THE EXPRESSION AND HALF-LIFE OF FREE HLA CLASS-I HEAVY-CHAINS UBIQUITOUSLY DETECTED AT THE CELL-SURFACE

A pool of free HLA class I chains has been detected at the plasma memb rane of all cells concomitantly expressing folded and assembled class I molecules. To determine the origin of these free HLA heavy chains, w e have examined the biosynthesis of a single HLA class I molecule, HLA -B27, expressed by a murine cell line (L-B27). In L-B27 cells, as prev iously shown in Epstein-Barr virus-transformed lymphoblastoid cell lin es, a precursor/product relationship exists. early in biosynthesis, be tween free (HC10-reactive) and beta-2-microglobulin (beta(2)m)-associa ted (W6/32-reactive) class I heavy chains as demonstrated by pulse/cha se experiments. At later stages in class I biosynthesis, both HC10- an d W6/32-reactive heavy chains display complex oligosaccharides and acc umulate at the cell surface. HC10- and W6/32-reactive molecules are bo th very stable at the cell surface, with half-lifes (t(1/2)) of > 7 h and similar to 4 h, respectively. Interestingly, cell surface expressi on and turnover of HC10- and W6/32-reactive molecules were affected by the addition of peptide ligands to the culture media. Culturing cells in the presence of HLA-B27 ligands resulted in the increased expressi on of W6/32-reactive molecules and the decreased expression of HC10-re active molecules. Moreover, addition of exogenous peptide extended the t(1/2) Of W6/32-reactive molecules to > 7 h and reduced that of HC10- reactive molecules to 4 h. These results indicate that surface HC10-re active molecules result largely from W6/32-reactive molecules followin g peptide and beta(2)m dissociation. Therefore, HC10-reactive species are not only the precursors but also the end products in class I biosy nthesis.