Assembly of MHC class I molecules in ex vivo carcinoma cells induced by IFN-gamma or by a binding peptide.
It has been reported that the assembly of MHC class I molecules in mutagenized cell lines could be induced by specific binding peptides. We have now demonstrated that the defect in assembly between heavy and light chains of class I molecules naturally occurred in tumor cells of one spontaneous ovarian carcinoma detected by one-dimensional isoelectric focusing of immunoprecipitates with anti-monomorphic class I MAb (W6/32) and by immunostaining with free heavy chain and beta 2m-specific MAbs. In vitro treatment of the tumor cells with IFN-gamma induced the assembly and surface expression of majority class I molecules (A2.1, B7, B15, Cw6, Cw7 out of A2.1, A2*, B7, B15, Cw6, Cw7). Moreover, assembly of A2 and Cw6 was induced by exposure of the tumor cells to a HLA A2-binding peptide K62 derived from influenza A matrix protein. Autologous blood T lymphocytes were activated in mixed lymphocyte-tumor cell culture (MLTC) by the IFN-gamma-treated but not by the unmanipulated tumor cells. Although activated lymphocytes damaged both IFN-gamma-treated and untreated tumor cells, the alpha class I MAb (W6/32) efficiently inhibited the lysis of IFN-gamma-treated targets, but not the untreated targets. These results indicate that the defect of MHC class I assembly may result in the escape of tumor cells from immune response.
Wang
P
P
Department of Tumor Biology, Karolinska Institute, Sweden.
Vánky
F
F
Végh
Z
Z
Persson
U
U
Hising
C
C
Klein
E
E
D000595:Amino Acid Sequence; D005260:Female; D015789:HLA-A2 Antigen / Q000032:analysis / Q000096:biosynthesis*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology
D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C075525:A2-binding peptide; D007371:Interferon-gamma