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HLA-E–dependent Presentation of Mtb-derived Antigen to Human CD8⁺ T Cells

Amy S. Heinzel¹, Jeff E. Grotzke^1,3, Rebecca A. Lines², Deborah A. Lewinsohn^2,3, Andria L. McNabb⁴, Daniel N. Streblow³, Veronique M. Braud⁵, Heather J. Grieser⁶, John T. Belisle⁶ and David M. Lewinsohn^1,3

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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