Differential contribution of TAP and tapasin to HLA class I antigen expression

Immunology
Alan Belicha-VillanuevaN Bangia

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.

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Citations

Oct 15, 2013·Journal of Pediatric Gastroenterology and Nutrition·Giovanni Di NardoLaura Stronati
Oct 20, 2009·Immunogenetics·Vilasack ThammavongsaMalini Raghavan
Jan 21, 2014·Annals of the American Thoracic Society·Paul Forsythe
Oct 27, 2011·Immunology Letters·Dilip ShresthaAttila Jenei
Jul 6, 2010·Human Immunology·Alan Belicha-VillanuevaNaveen Bangia
Aug 5, 2008·Trends in Immunology·Malini RaghavanLarry Robert Peters
Mar 28, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shirin AshrafSalim I Khakoo
Aug 28, 2015·Journal of Translational Medicine·Lena SokolAlessandro Lugli
May 3, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Syed Monem RizviMalini Raghavan
Aug 24, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathalie VigneronRalf M Leonhardt
Jan 26, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Syed Monem RizviMalini Raghavan

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