Bacterial glycolipids and analogs as antigens for CD1d-restricted NKT cells

authored by

Douglass Wu, Guo Wen Xing, Michael A. Poles, Amir Horowitz, Yuki Kinjo, Barbara Sullivan, Vera Bodmer-Narkevitch, Oliver Plettenburg, Mitchell Kronenberg, Moriya Tsuji, David D. Ho, Chi Huey Wong

Abstract

The CD1 family of proteins binds self and foreign glycolipids for presentation to CD1-restricted T cells. To identify previously uncharacterized active CD1 ligands, especially those of microbial origin, numerous glycolipids were synthesized and tested for their ability to stimulate mouse and human natural killer T (NKT) cells. They included analogs of the well known NKT cell agonist α-galactosyl ceramide (α-GalCer), bacterial glycolipids, and variations of the self-glycolipid, sulfatide. Bacterial glycolipids, α-galacturonosyl-ceramides from Sphingomonas wittichii, although structurally similar to α-GalCer, have significant differences in the sugar head group as well as the ceramide portion. The Sphingomonas glycosphingolipids (GSLs) and sulfatide variants were shown to activate human NKT cells as measured by IL-4 and IFN-γ secretion. Moreover, CD1d-dimer staining revealed human NKT cell reactivity toward these GSLs and to the sulfatides in a fashion comparable with α-GalCer. Because α-GalCer is a marine-sponge-derived ligand, our study here shows that bacterium-derived antigens are also able to stimulate mouse and human NKT cells.

External Organisation(s)

The Scripps Research Translational Institute
Rockefeller University
New York University (NYU)
La Jolla Institute for Allergy and Immunology

Type

Article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Volume

102

Pages

1351-1356

No. of pages

6

ISSN

0027-8424

Publication date

01.02.2005

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

General

Sustainable Development Goals

SDG 14 - Life Below Water

Electronic version(s)

https://doi.org/10.1073/pnas.0408696102 (Access: Open)