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.