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: Alan Belicha-Villanueva, Sarah McEvoy, Kelly Cycon, Soldano Ferrone, Sandra O Gollnick, Naveen Bangia
• Journal: Immunology (Immunology) Vol. 124 Issue 1 Pg. 112-20 (May 2008) ISSN: 1365-2567 [Electronic] England
• PMID: 18194274 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-Binding Cassette Transporters
• HLA-B Antigens
• Histocompatibility Antigens Class I
• Membrane Transport Proteins
• Neoplasm Proteins
• tapasin
• transporter associated with antigen processing (TAP)
• Interferon-gamma

Topics

• ATP-Binding Cassette Transporters (immunology)
• Antigen Presentation (immunology)
• Gene Expression Regulation (immunology)
• HLA-B Antigens (metabolism)
• Histocompatibility Antigens Class I (metabolism)
• Humans
• Interferon-gamma (immunology)
• Melanoma (immunology)
• Membrane Transport Proteins (immunology)
• Neoplasm Proteins (immunology)
• Transfection
• Tumor Cells, Cultured