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Cd1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection

Lookup NU author(s): Mark Guy, Professor Del Besra

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Abstract

T cells recognize microbial glycolipids presented by CD1 proteins, but there is no information regarding the generation of natural glycolipid antigens within infected tissues. Therefore, we determined the molecular basis of CD1b-restricted T cell recognition of mycobacterial glycosylated mycolates, including those produced during tissue infection in vivo. Transfection of the T cell receptor (TCR) α and β chains from a glucose monomycolate (GMM)-specific T cell line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This TCR-mediated response was highly specific for natural mycobacterial glucose-6-O-(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the stereochemistry of the mycolate lipid, and the linkage between the carbohydrate and the lipid. Mycobacterial production of antigenic GMM absolutely required a nonmycobacterial source of glucose that could be supplied by adding glucose to media at concentrations found in mammalian tissues or by infecting tissue in vivo. These results indicate that mycobacteria synthesized antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. Specific T cell recognition of an epitope formed by interaction of host and pathogen biosynthetic pathways provides a mechanism for immune response to those pathogenic mycobacteria that have productively infected tissues, as distinguished from ubiquitous, but innocuous, environmental mycobacteria.


Publication metadata

Author(s): Moody DB, Guy MR, Grant E, Cheng T-Y, Brenner MB, Besra GS, Porcelli SA

Publication type: Article

Publication status: Published

Journal: Journal of Experimental Medicine

Year: 2000

Volume: 192

Issue: 7

Pages: 965-976

ISSN (print): 0022-1007

ISSN (electronic): 1540-9538

Publisher: Rockefeller University Press

URL: http://dx.doi.org/10.1084/jem.192.7.965

DOI: 10.1084/jem.192.7.965

PubMed id: 11015438


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Funding

Funder referenceFunder name
AI40135NIAID NIH HHS
ARO1988NIAMS NIH HHS
AI45889NIAID NIH HHS
R01 AI045889NIAID NIH HHS

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