Submitted February 5, 2008
Accepted September 19, 2008
Regulation of HLA class I surface expression requires CD99 and p230/golgin-245 interaction
Aurore Bremond, Ophelie Meynet, Karim Mahiddine, Sylvie Coito, Melanie Tichet, Katia Scotlandi, Jean-Philippe Breittmayer, Pierre Gounon, Paul A. Gleeson, Alain Bernard, and Ghislaine Bernard*
INSERM UMR U576, Nice, France
Universite Nice-Sophia Antipolis, Nice, France
Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy
CHU Nice, Hopital de L'Archet, Laboratoire d'Immunologie, Nice, France
Centre Commun de Microscopie Faculte des Sciences, Nice, France
Department of Biochemistry and Molecular Biology and Bio21 Molecular Science, Biotechnology Institute, University of Melbourne, Melbourne, Australia
* Corresponding author; email: bernardg{at}unice.fr.
By presenting antigenic peptides on the cell surface, Human Leucocyte Antigen (HLA) class I molecules are critical for immune defence. 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-
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.
