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...
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Published in | Blood Vol. 113; no. 2; pp. 347 - 357 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
Elsevier Inc
08.01.2009
Americain Society of Hematology |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2008-02-137745 |