Regulation of HLA class I surface expression requires CD99 and p230/golgin-245 interaction

• Published in: Blood 2009-01, Vol.113 (2), p.347-357
• Main Authors: Brémond, Aurore, Meynet, Ophélie, Mahiddine, Karim, Coito, Sylvie, Tichet, Mélanie, Scotlandi, Katia, Breittmayer, Jean-Philippe, Gounon, Pierre, Gleeson, Paul A., Bernard, Alain, Bernard, Ghislaine
• Format: Article
• Language: English
• Subjects: 12E7 Antigen; Antigens, CD - immunology; Antigens, CD - metabolism; Antiviral Agents - immunology; Antiviral Agents - pharmacology; Autoantigens - immunology; Autoantigens - metabolism; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Cell physiology; Cytosol - immunology; Cytosol - metabolism; Fundamental and applied biological sciences. Psychology; Golgi Apparatus - immunology; Golgi Apparatus - metabolism; Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class I - immunology; HLA Antigens - biosynthesis; HLA Antigens - immunology; Humans; Immunity, Cellular - physiology; Interferon-gamma - immunology; Interferon-gamma - pharmacology; Jurkat Cells; Membrane and intracellular transports; Membrane Proteins - immunology; Membrane Proteins - metabolism; Molecular and cellular biology; Protein Structure, Tertiary - physiology; Protein Transport - drug effects; Protein Transport - immunology; Transport Vesicles - immunology; Transport Vesicles - metabolism; Up-Regulation - drug effects; Up-Regulation - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-02-137745

By presenting antigenic peptides on the cell surface, human leukocyte antigen (HLA) class I molecules are critical for immune defense. Their surface density determines, to a large extent, the level of CD8+ T cell–dependent immune reactions; their loss is a major mechanism of immune escape. Therefore, powerful processes should regulate their surface expression. Here we document the mechanisms used by CD99 to mediate HLA class I modulation. Up-regulation of HLA class I by IFN-γ requires CD99. In the trans Golgi network (TGN), and up to the cell surface, CD99 and HLA class I are physically associated via their transmembrane domain. CD99 also binds p230/golgin-245, a coiled-coil protein that recycles between the cytosol and buds/vesicles of the TGN and which plays a fundamental role in trafficking transport vesicles. p230/golgin-245 is anchored within TGN membranes via its Golgin-97, RanBP1, IMh1p, P230 (GRIP) domain and the overexpression of which leads to surface and intracellular down-modulation of HLA class I molecules.