Structural determination of lipid antigens captured at the CD1d–T-cell receptor interface

Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and the...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-08, Vol.114 (31), p.8348-8353
Main Authors: Brennan, Patrick J., Cheng, Tan-Yun, Pellicci, Daniel G., Watts, Gerald F.M., Veerapen, Natacha, Young, David C., Rossjohn, Jamie, Besra, Gurdyal S., Godfrey, Dale I., Brenner, Michael B., Moody, D. Branch
Format: Article
Language:English
Subjects:
Adipocytes
Antigens
Biochemical analysis
Biological Sciences
Carbohydrates
CD1d antigen
Cow's milk
Diet
Glycolipids
Lipids
Lymphocytes
Lymphocytes T
Mammals
Mass spectrometry
Mass spectroscopy
Microorganisms
Milk
Natural killer cells
Receptors
T cell receptors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and their unusual α-anomeric linkage has been thought to define a “foreign” lipid antigen motif. However, mammals use endogenous lipids to select iNKT cells, and there is compelling evidence for iNKT cell responses in various types of sterile inflammation. The nature of endogenous or environmental lipid antigens encountered by iNKT cells is not well defined. Here, we sought to identify lipid antigens in cow’s milk, a prominent part of the human diet. We developed a method to directly capture lipid antigens within CD1d–lipid–TCR complexes, while excluding CD1d bound to nonantigenic lipids, followed by direct biochemical analysis of the lipid antigens trapped at the TCR–CD1d interface. The specific antigens captured by this “TCR trap” method were identified as α-linked monohexosylceramides by mass spectrometry fragmentation patterns that distinguished α- from β-anomeric monohexosylceramides. These data provide direct biochemical evidence for α-linked lipid antigens from a common dietary source.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1705882114