Studies on binding of HIV-I p24(gag) peptide to HLA-Cw3(+) cells

Human major histocompatibility complex class I antigens, HLA-C, an expresse d on the cell surface at approximately a tenfold lower level than HLA-A and -B. We hypothesized that the expression of HLA-C is limited by the quantit y of high affinity peptides which bind to these molecules, thus allowing on ly a small fraction of HLA-C molecules to be transported and/or to remain s table on the cell surface. If this assumption is correct, then the addition of exogenous peptide should increase cell surface HLA-C expression. To ver ify the hypothesis, we pulsed lymphoblastoid cell line PAJ (HLA-Cw3(+)) wit h synthetic HIV-1 p24(gag) 145-152 peptide, known to be presented to T-lymp hocytes by HLA-Cw3 molecule. PAJ (HLA-Cw3(+)) cells bound approximately two times more of the peptide than HAJ (HLA-Cw3(-)). and four times more than 500/C9 (HLA-Cw3(-)) cells. Accordingly, overnight pulsing of PAJ cells with the p24(gag) 145-152 peptide caused an increase in class I HLA expression detected on the cell surface by how cytofluorimetric analysis with anti-HLA -B,C monoclonal antibodies but not by anti-HLA-A antibody. In contrast, HLA -Cw3(-) cells treated in the same manner did not show any increase of HLA c lass I expression. Our data suggest that low concentration of high affinity peptides within the cell may be one of the factors limiting cell surface e xpression of HLA-C molecules. (C) 1998 Elsevier Science B.V. All rights res erved.