CD1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection

D. Branch Moody, Mark R. Guy, Ethan Grant, Tan Yun Cheng, Michael B. Brenner, Gurdyal S. Besra, Steven A. Porcelli

Research output: Contribution to journalArticle

114 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)965-976
Number of pages12
JournalJournal of Experimental Medicine
Volume192
Issue number7
DOIs
StatePublished - Oct 2 2000
Externally publishedYes

Fingerprint

Glycolipids
Carbohydrates
T-Lymphocytes
Lipids
Antigens
Glucose
Mycobacterium
T-Cell Antigen Receptor
Infection
Carbohydrate Conformation
Host-Pathogen Interactions
T-Lymphocyte Epitopes
Biosynthetic Pathways
Transfection
Cell Line
glucose mycolate
Proteins

Keywords

  • Antigen presentation
  • CD1
  • Glucose monomycolate
  • Mycobacteria
  • T cell

ASJC Scopus subject areas

  • Immunology

Cite this

CD1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection. / Moody, D. Branch; Guy, Mark R.; Grant, Ethan; Cheng, Tan Yun; Brenner, Michael B.; Besra, Gurdyal S.; Porcelli, Steven A.

In: Journal of Experimental Medicine, Vol. 192, No. 7, 02.10.2000, p. 965-976.

Research output: Contribution to journalArticle

Moody, D. Branch ; Guy, Mark R. ; Grant, Ethan ; Cheng, Tan Yun ; Brenner, Michael B. ; Besra, Gurdyal S. ; Porcelli, Steven A. / CD1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection. In: Journal of Experimental Medicine. 2000 ; Vol. 192, No. 7. pp. 965-976.
@article{7d13e4e699624579a9ec0f2e24b62631,
title = "CD1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection",
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.",
keywords = "Antigen presentation, CD1, Glucose monomycolate, Mycobacteria, T cell",
author = "Moody, {D. Branch} and Guy, {Mark R.} and Ethan Grant and Cheng, {Tan Yun} and Brenner, {Michael B.} and Besra, {Gurdyal S.} and Porcelli, {Steven A.}",
year = "2000",
month = "10",
day = "2",
doi = "10.1084/jem.192.7.965",
language = "English (US)",
volume = "192",
pages = "965--976",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "7",

}

TY - JOUR

T1 - CD1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection

AU - Moody, D. Branch

AU - Guy, Mark R.

AU - Grant, Ethan

AU - Cheng, Tan Yun

AU - Brenner, Michael B.

AU - Besra, Gurdyal S.

AU - Porcelli, Steven A.

PY - 2000/10/2

Y1 - 2000/10/2

N2 - 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.

AB - 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.

KW - Antigen presentation

KW - CD1

KW - Glucose monomycolate

KW - Mycobacteria

KW - T cell

UR - http://www.scopus.com/inward/record.url?scp=0034596833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034596833&partnerID=8YFLogxK

U2 - 10.1084/jem.192.7.965

DO - 10.1084/jem.192.7.965

M3 - Article

C2 - 11015438

AN - SCOPUS:0034596833

VL - 192

SP - 965

EP - 976

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 7

ER -