The tetraspan protein EMP2 increases surface expression of class I major histocompatibility complex proteins and susceptibility to CTL-mediated cell death

Clin Immunol. 2003 May;107(2):129-36. doi: 10.1016/s1521-6616(03)00048-2.


Dysregulation of class I major histocompatibility (MHC1) expression is an important mechanism of immunologic resistance for certain virus-infected or neoplastic cells. This study characterizes a new molecule affecting MHC1 expression and CTL cytotoxicity. Epithelial membrane protein 2 (EMP2) is a tetraspan protein recently identified for its role in suppressing B lymphoma tumorigenicity. The biochemistry of EMP2 suggests that it regulates the surface expression of certain membrane proteins, notably those destined for lipid raft microdomains. In this study, retroviral overexpression of EMP2 in target cells increased their susceptibility to CTL cytotoxicity. Conversely, down-expression of EMP2 using an EMP2-specific ribozyme rendered target cells CTL-resistant. EMP2 expression increased the surface levels of MHC1, CD54, and GM1 glycolipids. Biochemical fractionation indicated that these molecules reside with EMP2 in a lipid raft membrane compartment. Among MHC1 proteins, surface display of H-2D was particularly dependent on EMP2 expression, and blocking antibodies demonstrated that H-2D was critical for allogeneic CTL recognition. This study demonstrates an unexpected role for a tetraspan protein in CTL-mediated cell death and MHC1 surface trafficking.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Communication / immunology
  • Flow Cytometry
  • G(M1) Ganglioside / immunology
  • G(M1) Ganglioside / metabolism
  • Gene Expression Regulation
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Immunoblotting
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Function-Associated Antigen-1 / biosynthesis
  • Membrane Glycoproteins / immunology*
  • Membrane Microdomains / immunology
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism


  • Emp2 protein, mouse
  • Histocompatibility Antigens Class I
  • Lymphocyte Function-Associated Antigen-1
  • Membrane Glycoproteins
  • Intercellular Adhesion Molecule-1
  • G(M1) Ganglioside