Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL

Nagendra R. Hegde, Claire Dunn, David Lewinsohn, Michael A. Jarvis, Jay Nelson, David Johnson

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB - expressed by adenovirus vectors or after HCMV infection - and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells. JEM

Original languageEnglish (US)
Pages (from-to)1109-1119
Number of pages11
JournalJournal of Cell Biology
Volume171
Issue number2
DOIs
StatePublished - Oct 24 2005

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CD4 Antigens
Glycoproteins
Endosomes
Neuroglia
T-Lymphocytes
Cytomegalovirus
Endothelial Cells
Epithelial Cells
Virus Assembly
Simplexvirus glycoprotein B
Cytomegalovirus Infections
Viral Proteins
Virus Diseases
Adenoviridae
Immunity
Membrane Proteins
Proteins
Peptide Hydrolases
Clone Cells
Antigens

ASJC Scopus subject areas

  • Cell Biology

Cite this

Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL. / Hegde, Nagendra R.; Dunn, Claire; Lewinsohn, David; Jarvis, Michael A.; Nelson, Jay; Johnson, David.

In: Journal of Cell Biology, Vol. 171, No. 2, 24.10.2005, p. 1109-1119.

Research output: Contribution to journalArticle

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