The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition

Stéphane Sidobre, Kirsten J L Hammond, Lise Bénazet-Sidobre, Sergei D. Maltsev, Stewart K. Richardson, Rachel M. Ndonye, Amy R. Howell, Teruyuki Sakai, Gurdyal S. Besra, Steven A. Porcelli, Mitchell Kronenberg

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Natural killer (NK) T cells with an invariant Vα14 rearrangement (Vα14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid α-galactosyl ceramide (α-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the Vα14i T cell antigen receptor (TCR) has a high affinity for the α-GalCer/CD1d complex, driven by a long half-life (t1/2). Although this result could have reflected the unique attributes of α-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of Vα14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t1/2. Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the Vα14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by Vα14i NKT cells.

Original languageEnglish (US)
Pages (from-to)12254-12259
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number33
DOIs
StatePublished - Aug 17 2004

Fingerprint

Glycosphingolipids
Natural Killer T-Cells
T-Cell Antigen Receptor
Antigens
Glycolipids
Galactosylceramides
Half-Life
T-Lymphocytes
Lipids
Population

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Sidobre, S., Hammond, K. J. L., Bénazet-Sidobre, L., Maltsev, S. D., Richardson, S. K., Ndonye, R. M., ... Kronenberg, M. (2004). The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition. Proceedings of the National Academy of Sciences of the United States of America, 101(33), 12254-12259. https://doi.org/10.1073/pnas.0404632101

The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition. / Sidobre, Stéphane; Hammond, Kirsten J L; Bénazet-Sidobre, Lise; Maltsev, Sergei D.; Richardson, Stewart K.; Ndonye, Rachel M.; Howell, Amy R.; Sakai, Teruyuki; Besra, Gurdyal S.; Porcelli, Steven A.; Kronenberg, Mitchell.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 33, 17.08.2004, p. 12254-12259.

Research output: Contribution to journalArticle

Sidobre, S, Hammond, KJL, Bénazet-Sidobre, L, Maltsev, SD, Richardson, SK, Ndonye, RM, Howell, AR, Sakai, T, Besra, GS, Porcelli, SA & Kronenberg, M 2004, 'The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 33, pp. 12254-12259. https://doi.org/10.1073/pnas.0404632101
Sidobre, Stéphane ; Hammond, Kirsten J L ; Bénazet-Sidobre, Lise ; Maltsev, Sergei D. ; Richardson, Stewart K. ; Ndonye, Rachel M. ; Howell, Amy R. ; Sakai, Teruyuki ; Besra, Gurdyal S. ; Porcelli, Steven A. ; Kronenberg, Mitchell. / The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 33. pp. 12254-12259.
@article{2d019eb33dba40669d2f5404e019b988,
title = "The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition",
abstract = "Natural killer (NK) T cells with an invariant Vα14 rearrangement (Vα14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid α-galactosyl ceramide (α-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the Vα14i T cell antigen receptor (TCR) has a high affinity for the α-GalCer/CD1d complex, driven by a long half-life (t1/2). Although this result could have reflected the unique attributes of α-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of Vα14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t1/2. Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the Vα14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by Vα14i NKT cells.",
author = "St{\'e}phane Sidobre and Hammond, {Kirsten J L} and Lise B{\'e}nazet-Sidobre and Maltsev, {Sergei D.} and Richardson, {Stewart K.} and Ndonye, {Rachel M.} and Howell, {Amy R.} and Teruyuki Sakai and Besra, {Gurdyal S.} and Porcelli, {Steven A.} and Mitchell Kronenberg",
year = "2004",
month = "8",
day = "17",
doi = "10.1073/pnas.0404632101",
language = "English (US)",
volume = "101",
pages = "12254--12259",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "33",

}

TY - JOUR

T1 - The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition

AU - Sidobre, Stéphane

AU - Hammond, Kirsten J L

AU - Bénazet-Sidobre, Lise

AU - Maltsev, Sergei D.

AU - Richardson, Stewart K.

AU - Ndonye, Rachel M.

AU - Howell, Amy R.

AU - Sakai, Teruyuki

AU - Besra, Gurdyal S.

AU - Porcelli, Steven A.

AU - Kronenberg, Mitchell

PY - 2004/8/17

Y1 - 2004/8/17

N2 - Natural killer (NK) T cells with an invariant Vα14 rearrangement (Vα14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid α-galactosyl ceramide (α-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the Vα14i T cell antigen receptor (TCR) has a high affinity for the α-GalCer/CD1d complex, driven by a long half-life (t1/2). Although this result could have reflected the unique attributes of α-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of Vα14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t1/2. Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the Vα14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by Vα14i NKT cells.

AB - Natural killer (NK) T cells with an invariant Vα14 rearrangement (Vα14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid α-galactosyl ceramide (α-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the Vα14i T cell antigen receptor (TCR) has a high affinity for the α-GalCer/CD1d complex, driven by a long half-life (t1/2). Although this result could have reflected the unique attributes of α-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of Vα14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t1/2. Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the Vα14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by Vα14i NKT cells.

UR - http://www.scopus.com/inward/record.url?scp=4344651706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4344651706&partnerID=8YFLogxK

U2 - 10.1073/pnas.0404632101

DO - 10.1073/pnas.0404632101

M3 - Article

C2 - 15304644

AN - SCOPUS:4344651706

VL - 101

SP - 12254

EP - 12259

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 - 33

ER -