RESTORED EXPRESSION OF MAJOR HISTOCOMPATIBILITY CLASS-I MOLECULES BY GENE-TRANSFER OF A PUTATIVE PEPTIDE TRANSPORTER

CYTOTOXIC T lymphocytes recognize antigen-derived peptides bound to major histocompatibility complex (MHC) class I molecules with which they assemble in the endoplasmic reticulum or in an undefined subcompartment 1-10. There is genetic evidence that the peptides that are products of cytosolic protein degradation are transported into this compartment by a peptide supply factor (PSF), encoded in the MHC class II region 11. Like the corresponding genes RING4, HAM1 and mtp1 (refs 12-14), PSF is related to the multidrug-resistance family of transporters 11 and may be a peptide pump, as translocation of peptides across membranes must occur independently of the secretory pathway 15. There is, however, no functional evidence for this role so far. Here we report gene transfer experiment showing that expression of PSF complementary DNA in the human lymphoblastoid cell line mutant 721.134 (refs 11, 16, 17) restores normal levels of surface HLA-A2 and -B5. No similar effect was observed in 721.174 mutant cells, in which a homozygous deletion includes PSF among several other closely linked genes 11. At least one of these genes may therefore also be required for PSF function.