REGULATION OF MHC CLASS-I MEMBRANE EXPRESSION BY BETA-2-MICROGLOBULIN

MHC-I binding peptides and beta2 microglobulin (beta2-m) can upregulat e the MHC-I heavy chain expression on certain peptide transporter muta nt cells. We have further studied this with normal cells and non-mutan t cell lines. No MHC-I upregulation was seen with normal, resting or a ctivated T cells. On mouse cell lines P815 and B16, both peptides and human beta2-m gave an additive upregulation response. With the human s mall cell lung carcinoma H82, an optimal HLA.A2 binding peptide (GILGF VFTL) gave an upregulation response, whereas beta2-m alone or in combi nation with this peptide had no effect. However, beta2-m potentiated t he response of H82 cells to a slightly longer peptide. Using mutant RM A-S cells, it was found that both Brefeldin A (BFA) and chloroquine, b ut not leupeptin, inhibited MHC-I upregulation response to both peptid e and beta2-m. In contrast to chloroquine, BFA also gave a reduction o f background membrane MHC-1 expression, presumably due to a block in G olgi transport. Human beta2-m, which binds to RMA-S cells, and which i s known to internalize into endosomes, did not reappear on the cell su rface. When D(b) on RMA-S cells was upregulated by human beta2-m, the sensitivity of these cells to D(b) restricted CTL cells increased. Eve n if beta2-m did not upregulate the overall MHC-I expression on normal cells, it may still quantitatively increase the expression of optimal ly presented peptides and endosomal recycling may be important in this process.