The murine cytomegalovirus immune evasion protein m4/gp34 forms biochemically distinct complexes with class I MHC at the cell surface and in a pre-golgi compartment

D. G. Kavanagh, U. H. Koszinowski, Ann Hill

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Abstract

We have recently demonstrated that the murine CMV (MCMV) gene m4 is an immune evasion gene that protects MCMV-infected targets from some virus-specific CTL, clones.m4 encodes m4/gp34, a 34-kDa glycoprotein that binds to major histocompatibility complex class I in the endoplasmic reticulum and forms a detergent-stable complex that is exported to the surface of the cell. To investigate how m4/gp34 promotes CTL evasion, we analyzed the assembly and export of m4/gp34-Kh complexes. We found that 50-70% of Kh exported over the course of MCMV infection was m4/gp34 associated. Because these complexes are present at the cell surface, it is possible that m4 mediates CTL evasion by interfering with contact between class I and receptors on the T cell. In addition, we found that Kb retained by the MCMV immune evasion gene m152 formed a novel type of complex with Endo H-sensitive m4/gp34; these complexes are distinguished from the exported complexes by being stable in 1% digitonin and unstable in 1% Nonidet P-40. Because this association occurs in a pre-Golgi compartment, m4/gp34 might also interfere with Ag presentation by affecting some aspect of class I assembly, such as peptide loading. Although m4/gp34 requires β2-microglobulin to bind class I, there was no significant binding of m4/gp34 to β2-microglobulin in the absence of class I H chain, demonstrating that m4/gp34 forms Nonidet P-40-stable complexes specifically with folded conformations of class I. We conclude that m4/gp34 promotes immune evasion by a novel mechanism involving altered assembly and/or T cell recognition of class I molecules.

Original languageEnglish (US)
Pages (from-to)3894-3902
Number of pages9
JournalJournal of Immunology
Volume167
Issue number7
StatePublished - Oct 1 2001

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Muromegalovirus
Immune Evasion
Genes
Digitonin
Proteins
T-Cell Antigen Receptor
Major Histocompatibility Complex
Endoplasmic Reticulum
Detergents
Glycoproteins
Clone Cells
Viruses
T-Lymphocytes
Peptides
Infection
Nonidet P-40

ASJC Scopus subject areas

  • Immunology

Cite this

The murine cytomegalovirus immune evasion protein m4/gp34 forms biochemically distinct complexes with class I MHC at the cell surface and in a pre-golgi compartment. / Kavanagh, D. G.; Koszinowski, U. H.; Hill, Ann.

In: Journal of Immunology, Vol. 167, No. 7, 01.10.2001, p. 3894-3902.

Research output: Contribution to journalArticle

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abstract = "We have recently demonstrated that the murine CMV (MCMV) gene m4 is an immune evasion gene that protects MCMV-infected targets from some virus-specific CTL, clones.m4 encodes m4/gp34, a 34-kDa glycoprotein that binds to major histocompatibility complex class I in the endoplasmic reticulum and forms a detergent-stable complex that is exported to the surface of the cell. To investigate how m4/gp34 promotes CTL evasion, we analyzed the assembly and export of m4/gp34-Kh complexes. We found that 50-70{\%} of Kh exported over the course of MCMV infection was m4/gp34 associated. Because these complexes are present at the cell surface, it is possible that m4 mediates CTL evasion by interfering with contact between class I and receptors on the T cell. In addition, we found that Kb retained by the MCMV immune evasion gene m152 formed a novel type of complex with Endo H-sensitive m4/gp34; these complexes are distinguished from the exported complexes by being stable in 1{\%} digitonin and unstable in 1{\%} Nonidet P-40. Because this association occurs in a pre-Golgi compartment, m4/gp34 might also interfere with Ag presentation by affecting some aspect of class I assembly, such as peptide loading. Although m4/gp34 requires β2-microglobulin to bind class I, there was no significant binding of m4/gp34 to β2-microglobulin in the absence of class I H chain, demonstrating that m4/gp34 forms Nonidet P-40-stable complexes specifically with folded conformations of class I. We conclude that m4/gp34 promotes immune evasion by a novel mechanism involving altered assembly and/or T cell recognition of class I molecules.",
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