Structural requirements for antigen presentation by mouse CD1

Nicolas Burdin, Laurent Brossay, Massimo Degano, Hiroshi Iijima, Ming Gui, Ian A. Wilson, Mitchell Kronenberg

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

The structural basis for the T cell response to glycolipid antigens (Ags) remains poorly understood. T lymphocytes autoreactive for mouse CD1 (mCD1.1) or reactive for the glycosphingolipid α-galactosylceramide (α-GalCer) presented by mCD1.1 have been described previously. In this paper it is shown that mutations at the top of the α helices and in the bottom of the Ag-binding groove can disrupt both mCD1.1 autoreactivity and α-GalCer recognition. The locations of the positions that affect T cell responses indicate that recognition of mCD1.1 is not likely to be unconventional or superantigen-like. Furthermore, the effects of the bottom of the pocket mutation suggest that the autoreactive response could require an autologous ligand, and they indicate that α-GalCer binds to the groove of mCD1.1, most likely with the shorter 18-carbon hydrophobic chain in the A' pocket. Natural killer T cell hybridomas with identical T cell antigen receptor (TCR) α chains and different β chains respond differently to α-GalCer presented by mCD1.1 mutants. This finding indicates a role for TCR β in defining natural killer T cell specificity, despite the more restricted diversity of the α chains in these cells. Overall, the data are consistent with a mode of lipoglycan recognition similar to that proposed for glycopeptides, in which the TCR α and β chains survey a surface composed of both mCD1.1 and the carbohydrate portion of α-GalCer.

Original languageEnglish
Pages (from-to)10156-10161
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number18
Publication statusPublished - Aug 29 2000

Fingerprint

Antigen Presentation
T-Cell Antigen Receptor
Natural Killer T-Cells
T-Lymphocytes
T-Cell Antigen Receptor Specificity
Galactosylceramides
Superantigens
Glycosphingolipids
Mutation
Glycopeptides
Glycolipids
Hybridomas
Lipopolysaccharides
Carbon
Carbohydrates
Ligands
Antigens

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Burdin, N., Brossay, L., Degano, M., Iijima, H., Gui, M., Wilson, I. A., & Kronenberg, M. (2000). Structural requirements for antigen presentation by mouse CD1. Proceedings of the National Academy of Sciences of the United States of America, 97(18), 10156-10161.

Structural requirements for antigen presentation by mouse CD1. / Burdin, Nicolas; Brossay, Laurent; Degano, Massimo; Iijima, Hiroshi; Gui, Ming; Wilson, Ian A.; Kronenberg, Mitchell.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 18, 29.08.2000, p. 10156-10161.

Research output: Contribution to journalArticle

Burdin, N, Brossay, L, Degano, M, Iijima, H, Gui, M, Wilson, IA & Kronenberg, M 2000, 'Structural requirements for antigen presentation by mouse CD1', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 18, pp. 10156-10161.
Burdin, Nicolas ; Brossay, Laurent ; Degano, Massimo ; Iijima, Hiroshi ; Gui, Ming ; Wilson, Ian A. ; Kronenberg, Mitchell. / Structural requirements for antigen presentation by mouse CD1. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 18. pp. 10156-10161.
@article{ebe9722870a84a76b9b78504cec30d47,
title = "Structural requirements for antigen presentation by mouse CD1",
abstract = "The structural basis for the T cell response to glycolipid antigens (Ags) remains poorly understood. T lymphocytes autoreactive for mouse CD1 (mCD1.1) or reactive for the glycosphingolipid α-galactosylceramide (α-GalCer) presented by mCD1.1 have been described previously. In this paper it is shown that mutations at the top of the α helices and in the bottom of the Ag-binding groove can disrupt both mCD1.1 autoreactivity and α-GalCer recognition. The locations of the positions that affect T cell responses indicate that recognition of mCD1.1 is not likely to be unconventional or superantigen-like. Furthermore, the effects of the bottom of the pocket mutation suggest that the autoreactive response could require an autologous ligand, and they indicate that α-GalCer binds to the groove of mCD1.1, most likely with the shorter 18-carbon hydrophobic chain in the A' pocket. Natural killer T cell hybridomas with identical T cell antigen receptor (TCR) α chains and different β chains respond differently to α-GalCer presented by mCD1.1 mutants. This finding indicates a role for TCR β in defining natural killer T cell specificity, despite the more restricted diversity of the α chains in these cells. Overall, the data are consistent with a mode of lipoglycan recognition similar to that proposed for glycopeptides, in which the TCR α and β chains survey a surface composed of both mCD1.1 and the carbohydrate portion of α-GalCer.",
author = "Nicolas Burdin and Laurent Brossay and Massimo Degano and Hiroshi Iijima and Ming Gui and Wilson, {Ian A.} and Mitchell Kronenberg",
year = "2000",
month = "8",
day = "29",
language = "English",
volume = "97",
pages = "10156--10161",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "18",

}

TY - JOUR

T1 - Structural requirements for antigen presentation by mouse CD1

AU - Burdin, Nicolas

AU - Brossay, Laurent

AU - Degano, Massimo

AU - Iijima, Hiroshi

AU - Gui, Ming

AU - Wilson, Ian A.

AU - Kronenberg, Mitchell

PY - 2000/8/29

Y1 - 2000/8/29

N2 - The structural basis for the T cell response to glycolipid antigens (Ags) remains poorly understood. T lymphocytes autoreactive for mouse CD1 (mCD1.1) or reactive for the glycosphingolipid α-galactosylceramide (α-GalCer) presented by mCD1.1 have been described previously. In this paper it is shown that mutations at the top of the α helices and in the bottom of the Ag-binding groove can disrupt both mCD1.1 autoreactivity and α-GalCer recognition. The locations of the positions that affect T cell responses indicate that recognition of mCD1.1 is not likely to be unconventional or superantigen-like. Furthermore, the effects of the bottom of the pocket mutation suggest that the autoreactive response could require an autologous ligand, and they indicate that α-GalCer binds to the groove of mCD1.1, most likely with the shorter 18-carbon hydrophobic chain in the A' pocket. Natural killer T cell hybridomas with identical T cell antigen receptor (TCR) α chains and different β chains respond differently to α-GalCer presented by mCD1.1 mutants. This finding indicates a role for TCR β in defining natural killer T cell specificity, despite the more restricted diversity of the α chains in these cells. Overall, the data are consistent with a mode of lipoglycan recognition similar to that proposed for glycopeptides, in which the TCR α and β chains survey a surface composed of both mCD1.1 and the carbohydrate portion of α-GalCer.

AB - The structural basis for the T cell response to glycolipid antigens (Ags) remains poorly understood. T lymphocytes autoreactive for mouse CD1 (mCD1.1) or reactive for the glycosphingolipid α-galactosylceramide (α-GalCer) presented by mCD1.1 have been described previously. In this paper it is shown that mutations at the top of the α helices and in the bottom of the Ag-binding groove can disrupt both mCD1.1 autoreactivity and α-GalCer recognition. The locations of the positions that affect T cell responses indicate that recognition of mCD1.1 is not likely to be unconventional or superantigen-like. Furthermore, the effects of the bottom of the pocket mutation suggest that the autoreactive response could require an autologous ligand, and they indicate that α-GalCer binds to the groove of mCD1.1, most likely with the shorter 18-carbon hydrophobic chain in the A' pocket. Natural killer T cell hybridomas with identical T cell antigen receptor (TCR) α chains and different β chains respond differently to α-GalCer presented by mCD1.1 mutants. This finding indicates a role for TCR β in defining natural killer T cell specificity, despite the more restricted diversity of the α chains in these cells. Overall, the data are consistent with a mode of lipoglycan recognition similar to that proposed for glycopeptides, in which the TCR α and β chains survey a surface composed of both mCD1.1 and the carbohydrate portion of α-GalCer.

UR - http://www.scopus.com/inward/record.url?scp=0034730119&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034730119&partnerID=8YFLogxK

M3 - Article

VL - 97

SP - 10156

EP - 10161

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

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

SN - 0027-8424

IS - 18

ER -