Journal
IMMUNOLOGY
Volume 124, Issue 1, Pages 112-120Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1365-2567.2007.02746.x
Keywords
antigen presentation; cancer; human leucocyte antigen; major histocompatibility complex; tapasin; transporter associated with antigen processing (TAP); tumour
Categories
Funding
- NCI NIH HHS [CA98156, CA105500, CA016156, P01 CA109688, R01 CA110249, CA55791, CA67108, R01 CA105500, R01 CA067108, R01 CA098156, P01 CA055791, R01 CA138188] Funding Source: Medline
- NIAID NIH HHS [AI063341, R21 AI071183-02] Funding Source: Medline
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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.
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