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. 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. Like the corresponding genes RING4, HAM1 and mtp1, PSF is related to the multidrug-resistance family of transporters and may be a peptide pump, as translocation of peptides across membranes must occur independently of the secretory pathway. There is, however, no functional evidence for this role so far. Here we report gene transfer experiments showing that expression of PSF complementary DNA in the human lymphoblastoid cell line mutant 721.134 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. At least one of these genes may therefore also be required for PSF function.
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Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
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D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D015870:Gene Expression; D005805:Genes, MHC Class I; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
D002352:Carrier Proteins; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger