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

Blood. 2009 Jan 8;113(2):347-57. doi: 10.1182/blood-2008-02-137745. Epub 2008 Oct 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12E7 Antigen
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antiviral Agents / immunology
  • Antiviral Agents / pharmacology
  • Autoantigens / immunology*
  • Autoantigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Cytosol / immunology
  • Cytosol / metabolism
  • Golgi Apparatus / immunology*
  • Golgi Apparatus / metabolism
  • HLA Antigens / biosynthesis
  • HLA Antigens / immunology
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunity, Cellular / physiology
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Jurkat Cells
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Protein Structure, Tertiary / physiology
  • Protein Transport / drug effects
  • Protein Transport / immunology
  • Transport Vesicles / immunology
  • Transport Vesicles / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / immunology*

Substances

  • 12E7 Antigen
  • Antigens, CD
  • Antiviral Agents
  • Autoantigens
  • CD99 protein, human
  • Cell Adhesion Molecules
  • GOLGA4 protein, human
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Interferon-gamma