TY - JOUR
T1 - The human CD1-restricted T cell repertoire is limited to cross-reactive antigens
T2 - Implications for host responses against immunologically related pathogens
AU - Sieling, Peter A.
AU - Torrelles, Jordi B.
AU - Stenger, Steffen
AU - Chung, Woosin
AU - Burdick, Anne E.
AU - Rea, Thomas H.
AU - Brennan, Patrick J.
AU - Belisle, John T.
AU - Porcelli, Steven A.
AU - Modlin, Robert L.
PY - 2005/3/1
Y1 - 2005/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20044392841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20044392841&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.174.5.2637
DO - 10.4049/jimmunol.174.5.2637
M3 - Article
C2 - 15728470
AN - SCOPUS:20044392841
SN - 0022-1767
VL - 174
SP - 2637
EP - 2644
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -