The human CD1-restricted T cell repertoire is limited to cross-reactive antigens

Implications for host responses against immunologically related pathogens

Peter A. Sieling, Jordi B. Torrelles, Steffen Stenger, Woosin Chung, Anne Burdick, Thomas H. Rea, Patrick J. Brennan, John T. Belisle, Steven A. Porcelli, Robert L. Modlin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2637-2644
Number of pages8
JournalJournal of Immunology
Volume174
Issue number5
StatePublished - Mar 1 2005

Fingerprint

T-Lymphocytes
Antigens
Mycobacterium leprae
Lipids
Clone Cells
Mycobacterium tuberculosis
Tuberculoid Leprosy
Lepromatous Leprosy
Species Specificity
Peptides
Leprosy
Mycobacterium
Tuberculosis
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

The human CD1-restricted T cell repertoire is limited to cross-reactive antigens : Implications for host responses against immunologically related pathogens. / Sieling, Peter A.; Torrelles, Jordi B.; Stenger, Steffen; Chung, Woosin; Burdick, Anne; Rea, Thomas H.; Brennan, Patrick J.; Belisle, John T.; Porcelli, Steven A.; Modlin, Robert L.

In: Journal of Immunology, Vol. 174, No. 5, 01.03.2005, p. 2637-2644.

Research output: Contribution to journalArticle

Sieling, PA, Torrelles, JB, Stenger, S, Chung, W, Burdick, A, Rea, TH, Brennan, PJ, Belisle, JT, Porcelli, SA & Modlin, RL 2005, 'The human CD1-restricted T cell repertoire is limited to cross-reactive antigens: Implications for host responses against immunologically related pathogens', Journal of Immunology, vol. 174, no. 5, pp. 2637-2644.
Sieling, Peter A. ; Torrelles, Jordi B. ; Stenger, Steffen ; Chung, Woosin ; Burdick, Anne ; Rea, Thomas H. ; Brennan, Patrick J. ; Belisle, John T. ; Porcelli, Steven A. ; Modlin, Robert L. / The human CD1-restricted T cell repertoire is limited to cross-reactive antigens : Implications for host responses against immunologically related pathogens. In: Journal of Immunology. 2005 ; Vol. 174, No. 5. pp. 2637-2644.
@article{8da0d8ae8748447c9dfcb2c39a3bc9a0,
title = "The human CD1-restricted T cell repertoire is limited to cross-reactive antigens: Implications for host responses against immunologically related pathogens",
abstract = "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.",
author = "Sieling, {Peter A.} and Torrelles, {Jordi B.} and Steffen Stenger and Woosin Chung and Anne Burdick and Rea, {Thomas H.} and Brennan, {Patrick J.} and Belisle, {John T.} and Porcelli, {Steven A.} and Modlin, {Robert L.}",
year = "2005",
month = "3",
day = "1",
language = "English",
volume = "174",
pages = "2637--2644",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

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

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

M3 - Article

VL - 174

SP - 2637

EP - 2644

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -