title: Differential contribution of TAP and tapasin to HLA class I antigen expression.
abstract: Expression of class I human leucocyte antigens (HLA) on the surface of malignant cells is critical for their recognition and destruction by cytotoxic T lymphocytes. Surface expression requires assembly and folding of HLA class I molecules in the endoplasmic reticulum with the assistance of proteins such as Transporter associated with Antigen Processing (TAP) and tapasin. Interferon-gamma induces both TAP and tapasin so dissection of which protein contributes more to HLA class I expression has not been possible previously. In this study, we take advantage of a human melanoma cell line in which TAP can be induced, but tapasin cannot. Interferon-gamma increases TAP protein levels dramatically but HLA class I expression at the cell surface does not increase substantially, indicating that a large increase in peptide supply is not sufficient to increase HLA class I expression. On the other hand, transfection of either allelic form of tapasin (R240 or T240) enhances HLA-B*5001 and HLA-B*5701 antigen expression considerably with only a modest increase in TAP. Together, these data indicate that in the presence of minimal TAP activity, tapasin can promote substantial HLA class I expression at the cell surface.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Belicha-Villanueva
authors.forename: Sarah
authors.initials: S
authors.lastname: McEvoy
authors.forename: Kelly
authors.initials: K
authors.lastname: Cycon
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Sandra O
authors.initials: SO
authors.lastname: Gollnick
authors.forename: Naveen
authors.initials: N
authors.lastname: Bangia
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D015235:HLA-B Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D026901:Membrane Transport Proteins / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018528:ATP-Binding Cassette Transporters; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; C107762:tapasin; C477327:transporter associated with antigen processing (TAP); D007371:Interferon-gamma