The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 2 October 2000.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 329K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moody, D. B.
Right arrow Articles by Porcelli, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moody, D. B.
Right arrow Articles by Porcelli, S. A.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2000/10/965/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 7, October 2, 2000 965-976

Original Article

Cd1b-Mediated T Cell Recognition of a Glycolipid Antigen Generated from Mycobacterial Lipid and Host Carbohydrate during Infection

D. Branch Moodya, Mark R. Guyb, Ethan Granta, Tan-Yun Chenga, Michael B. Brennera, Gurdyal S. Besrab, and Steven A. Porcellia

a Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
b School of Microbiological, Immunological and Virological Sciences, University of Newcastle upon Tyne, The Medical School, NE2 4HH Newcastle upon Tyne, United Kingdom
Smith Building Rm. 514, 1 Jimmy Fund Way, Boston, MA 02115.617-525-1010617-525-1037

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) {alpha} 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.

Key Words: CD1 • T cell • antigen presentation • mycobacteria • glucose monomycolate

Abbreviations used in this paper: GMM, glucose monomycolate; G-6-MM, C32 glucose-6-O-monomycolate; G-3-MM, glucose-3-O-monomycolate; MAME, mycolic acid methyl ester; Myc PL, mycolylphospholipid; NMR, nuclear magnetic resonance; Rf, retardation factor.

S.A. Porcelli's present address is The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Rm. 416 Forchheimer Bldg., 1300 Morris Park Ave., Bronx, NY 10461.

© 2000 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS