Differential contribution of TAP and tapasin to HLA class I antigen expression
Year: 2008
Type: article
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.
Source: Immunology
Institution: Roswell Park Comprehensive Cancer Center
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Antigen processing and HLA-peptide complexes in head and neck cancer, Combinatorial targeting of melanoma initiating cells, G1663496006, PDT Optimization and Mechanisms, HLA CLASS I PEPTIDE COMPLEX ADNORMALITIES IN MELANOMA, Rational Design of HMW-MAA Peptide Mimics, G6016253002, Regulation of Antigen Presentation by the Peptide Loading Complex, Immune Escape in Human Cancer: Mechanisms and Therapeutic Implications, PHOTODYNAMIC THERAPY (PDT) AND TUMOR IMMUNITY
OpenAlex ID: W1995809457