Regulation of HLA class I surface expression requires CD99 and p230/golgin-245 interaction.
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-gamma 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.
Brémond
Aurore
A
Inserm UMR 576, Nice, France.
Meynet
Ophélie
O
Mahiddine
Karim
K
Coito
Sylvie
S
Tichet
Mélanie
M
Scotlandi
Katia
K
Breittmayer
Jean-Philippe
JP
Gounon
Pierre
P
Gleeson
Paul A
PA
Bernard
Alain
A
Bernard
Ghislaine
G
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D006056:Golgi Apparatus / Q000276:immunology* / Q000378:metabolism; D006680:HLA Antigens / Q000096:biosynthesis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology; D022161:Transport Vesicles / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000071443:12E7 Antigen; D015703:Antigens, CD; D000998:Antiviral Agents; D001324:Autoantigens; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; C098772:GOLGA4 protein, human; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007371:Interferon-gamma