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The Human CD1-Restricted T Cell Repertoire Is Limited to Cross-Reactive Antigens: Implications for Host Responses against Immunologically Related Pathogens¹

Peter A. Sieling^2,*, Jordi B. Torrelles, Steffen Stenger^¶, Woosin Chung^*, Anne E. Burdick^||, Thomas H. Rea^#, Patrick J. Brennan, John T. Belisle, Steven A. Porcelli^** and Robert L. Modlin^*,,

^* Division of Dermatology, Department of Microbiology and Immunology, and Molecular Biology Institute, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA 90095; Department of Microbiology, Immunology, and Pathology College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523; ^¶ Institute for Clinical Microbiology, Immunology, and Hygiene, Universität Erlangen, Erlangen, Germany; ^|| Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL 33101; ^# Section of Dermatology, Keck School of Medicine at University of Southern California, Los Angeles, CA 90033; and ^** Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461

The repertoires of CD1- and MHC-restricted T cells are complementary, permitting the immune recognition of both lipid and peptide Ags, respectively. To compare the breadth of the CD1-restricted and MHC-restricted T cell repertoires, we evaluated T cell responses against lipid and peptide Ags of mycobacteria in leprosy, comparing tuberculoid patients, who are able to restrict the pathogen, and lepromatous patients, who have disseminated infection. The striking finding was that in lepromatous leprosy, T cells did not efficiently recognize lipid Ags from the leprosy pathogen, Mycobacterium leprae, or the related species, Mycobacterium tuberculosis, yet were able to efficiently recognize peptide Ags from M. tuberculosis, but not M. leprae. To identify a mechanism for T cell unresponsiveness against mycobacterial lipid Ags in lepromatous patients, we used T cell clones to probe the species specificity of the Ags recognized. We found that the majority of M. leprae-reactive CD1-restricted T cell clones (92%) were cross-reactive for multiple mycobacterial species, whereas the majority of M. leprae-reactive MHC-restricted T cells were species specific (66%), with a limited number of T cell clones cross-reactive (34%) with M. tuberculosis. In comparison with the MHC class II-restricted T cell repertoire, the CD1-restricted T cell repertoire is limited to recognition of cross-reactive Ags, imparting a distinct role in the host response to immunologically related pathogens.

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The JI 2005 174: 2447-2449. [Full Text]  

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				D. J. Lee, P. A. Sieling, M. T. Ochoa, S. R. Krutzik, B. Guo, M. Hernandez, T. H. Rea, G. Cheng, M. Colonna, and R. L. Modlin LILRA2 Activation Inhibits Dendritic Cell Differentiation and Antigen Presentation to T Cells J. Immunol., December 15, 2007; 179(12): 8128 - 8136. [Abstract] [Full Text] [PDF]