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

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

In: National Academy of Sciences. Proceedings, 17.07.2017.

Research output: Contribution to journalArticlepeer-review

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APA

Brennan, P. J., Cheng, T-Y., Pellicci, D. G., Watts, G. F. M., Veerapen, N., Young, D. C., Rossjohn, J., Besra, G. S., Godfrey, D. I., Brenner, M. B., & Moody, D. B. (2017). Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface. National Academy of Sciences. Proceedings. https://doi.org/10.1073/pnas.1705882114

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Author

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. / Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface. In: National Academy of Sciences. Proceedings. 2017.

Bibtex

@article{61a629989cc34ec69e06404125d21fad,
title = "Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface",
abstract = "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.",
keywords = "NKT, iNKT, lipid antigen, CD1d, glycolipid",
author = "Brennan, {Patrick J} and Tan-Yun Cheng and Pellicci, {Daniel G} and Watts, {Gerald F M} and Natacha Veerapen and Young, {David C} and Jamie Rossjohn and Besra, {Gurdyal S} and Godfrey, {Dale I} and Brenner, {Michael B} and Moody, {D Branch}",
year = "2017",
month = jul,
day = "17",
doi = "10.1073/pnas.1705882114",
language = "English",
journal = "Proceedings of the National Academy of Sciences",
issn = "1091-6490",
publisher = "National Academy of Sciences",

}

RIS

TY - JOUR

T1 - Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface

AU - Brennan, Patrick J

AU - Cheng, Tan-Yun

AU - Pellicci, Daniel G

AU - Watts, Gerald F M

AU - Veerapen, Natacha

AU - Young, David C

AU - Rossjohn, Jamie

AU - Besra, Gurdyal S

AU - Godfrey, Dale I

AU - Brenner, Michael B

AU - Moody, D Branch

PY - 2017/7/17

Y1 - 2017/7/17

N2 - 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.

AB - 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.

KW - NKT

KW - iNKT

KW - lipid antigen

KW - CD1d

KW - glycolipid

U2 - 10.1073/pnas.1705882114

DO - 10.1073/pnas.1705882114

M3 - Article

C2 - 28716901

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

ER -