The Journal of Experimental Medicine
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Published online 25 November 2002 doi:10.1084/jem.20020609
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© Rockefeller University Press, 0022-1007/2002/12/1473/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 11, December 2, 2002 1473-1481
HLA-E–dependent Presentation of Mtb-derived Antigen to Human CD8+ T Cells

Amy S. Heinzel1, Jeff E. Grotzke1,3, Rebecca A. Lines2, Deborah A. Lewinsohn2,3, Andria L. McNabb4, Daniel N. Streblow3, Veronique M. Braud5, Heather J. Grieser6, John T. Belisle6 and David M. Lewinsohn1,3

1 Division of Pulmonary & Critical Care Medicine, Portland VA Medical Center, the
2 Division of Pediatrics, Oregon Health Sciences University, Portland, OR 97201
3 Dept. of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201
4 Corixa Corporation, Seattle, WA 98104
5 Institut de Pharmacologie Moléculaire et Cellulaire, CNRS Sophia Antipolis, 06560 Paris, France
6 Mycobacteria Research Laboratories, Dept. of Microbiology, Colorado State University, Fort Collins, CO 80523

Address correspondence to David Lewinsohn, Pulmonary & CCM, PVAMC/OHSU, R&D 11, 3710 SW US Veterans Rd., Portland, OR 97201. Phone: 503-721-1020; Fax: 503-402-2816; E-mail: lewinsod{at}ohsu.edu

Previous studies in mice and humans have suggested an important role for CD8+ T cells in host defense to Mtb. Recently, we have described human, Mtb-specific CD8+ cells that are neither HLA-A, B, or C nor group 1 CD1 restricted, and have found that these cells comprise the dominant CD8+ T cell response in latently infected individuals. In this report, three independent methods are used to demonstrate the ability of these cells to recognize Mtb-derived antigen in the context of the monomorphic HLA-E molecule. This is the first demonstration of the ability of HLA-E to present pathogen-derived antigen. Further definition of the HLA-E specific response may aid development of an effective vaccine against tuberculosis.

Key Words: CD8-positive T lymphocytes • HLA-E • human • Mycobacterium tuberculosis


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