The Journal of Experimental Medicine
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Published online 10 October 2005 doi:10.1084/jem.20050162
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 8, 1109-1119
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ARTICLE

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

Nagendra R. Hegde1, Claire Dunn1, David M. Lewinsohn2, Michael A. Jarvis3, Jay A. Nelson1,3, and David C. Johnson1

1 Department of Molecular Microbiology and Immunology, Veterans Affairs Medical Center
2 Division of Pulmonary and Critical Care Medicine, Veterans Affairs Medical Center
3 Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR 97239

CORRESPONDENCE David C. Johnson: johnsoda{at}ohsu.edu

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.

Abbreviations used: Ad, adenovirus; BAC, bacterial artificial chromosome; CT, cytoplasmic tail; gB, glycoprotein B; gH, glycoprotein H; HCMV, human CMV; LCL, lymphoblastoid cell line; TAP, transporter associated with antigen presentation; TB, tuberculosis; TGN, trans-Golgi network; US, unique short.

N.R. Hegde and C. Dunn contributed equally to this work.


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