Human autoreactive T cells recognize CD1b and phospholipids

Ildiko Van Rhijn*, Twan Van Berlo, Tamara Hilmenyuk, Tan Yun Cheng, Benjamin J. Wolf, Raju V.V. Tatituri, Adam P. Uldrich, Giorgio Napolitani, Vincenzo Cerundolo, John D. Altman, Peter Willemsen, Shouxiong Huang, Jamie Rossjohn, Gurdyal S. Besra, M.B. Brenner, Dale I. Godfrey, D.B. Moody

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Scopus)

Abstract

In contrast with the common detection of T cells that recognize MHC, CD1a, CD1c, or CD1d proteins, CD1b autoreactive T cells have been difficult to isolate in humans. Here we report the development of polyvalent complexes of CD1b proteins and carbohydrate backbones (dextramers) and their use in identifying CD1b autoreactive T cells from human donors. Activation is mediated by αβ T-cell receptors (TCRs) binding to CD1b-phospholipid complexes, which is sufficient to activate autoreactive responses to CD1b-expressing cells. Using mass spectrometry and T-cell responses to scan through the major classes of phospholipids, we identified phosphatidylglycerol (PG) as the immunodominant lipid antigen. T cells did not discriminate the chemical differences that distinguish mammalian PG from bacterial PG. Whereas most models of T-cell recognition emphasize TCR discrimination of differing self and foreign structures, CD1b autoreactive T cells recognize lipids with dual self and foreign origin. PG is rare in the cellular membranes that carry CD1b proteins. However, bacteria and mitochondria are rich in PG, so these data point to a more general mechanism of immune detection of infection- or stressassociated lipids.

Original languageEnglish
Pages (from-to)380-385
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number2
DOIs
Publication statusPublished - 2016

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Phosphatidylglycerols
Phospholipids
T-Lymphocytes
T-Cell Antigen Receptor
Lipids
Immunodominant Epitopes
Proteins
Mass Spectrometry
Mitochondria
Carbohydrates
Bacteria
Membranes
Infection

Keywords

  • CD1b
  • Dendritic cell
  • Lipid antigen
  • Self-antigen
  • T cell

Cite this

Van Rhijn, I., Van Berlo, T., Hilmenyuk, T., Cheng, T. Y., Wolf, B. J., Tatituri, R. V. V., ... Moody, D. B. (2016). Human autoreactive T cells recognize CD1b and phospholipids. Proceedings of the National Academy of Sciences of the United States of America, 113(2), 380-385. https://doi.org/10.1073/pnas.1520947112
Van Rhijn, Ildiko ; Van Berlo, Twan ; Hilmenyuk, Tamara ; Cheng, Tan Yun ; Wolf, Benjamin J. ; Tatituri, Raju V.V. ; Uldrich, Adam P. ; Napolitani, Giorgio ; Cerundolo, Vincenzo ; Altman, John D. ; Willemsen, Peter ; Huang, Shouxiong ; Rossjohn, Jamie ; Besra, Gurdyal S. ; Brenner, M.B. ; Godfrey, Dale I. ; Moody, D.B. / Human autoreactive T cells recognize CD1b and phospholipids. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 2. pp. 380-385.
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title = "Human autoreactive T cells recognize CD1b and phospholipids",
abstract = "In contrast with the common detection of T cells that recognize MHC, CD1a, CD1c, or CD1d proteins, CD1b autoreactive T cells have been difficult to isolate in humans. Here we report the development of polyvalent complexes of CD1b proteins and carbohydrate backbones (dextramers) and their use in identifying CD1b autoreactive T cells from human donors. Activation is mediated by αβ T-cell receptors (TCRs) binding to CD1b-phospholipid complexes, which is sufficient to activate autoreactive responses to CD1b-expressing cells. Using mass spectrometry and T-cell responses to scan through the major classes of phospholipids, we identified phosphatidylglycerol (PG) as the immunodominant lipid antigen. T cells did not discriminate the chemical differences that distinguish mammalian PG from bacterial PG. Whereas most models of T-cell recognition emphasize TCR discrimination of differing self and foreign structures, CD1b autoreactive T cells recognize lipids with dual self and foreign origin. PG is rare in the cellular membranes that carry CD1b proteins. However, bacteria and mitochondria are rich in PG, so these data point to a more general mechanism of immune detection of infection- or stressassociated lipids.",
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Van Rhijn, I, Van Berlo, T, Hilmenyuk, T, Cheng, TY, Wolf, BJ, Tatituri, RVV, Uldrich, AP, Napolitani, G, Cerundolo, V, Altman, JD, Willemsen, P, Huang, S, Rossjohn, J, Besra, GS, Brenner, MB, Godfrey, DI & Moody, DB 2016, 'Human autoreactive T cells recognize CD1b and phospholipids', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 2, pp. 380-385. https://doi.org/10.1073/pnas.1520947112

Human autoreactive T cells recognize CD1b and phospholipids. / Van Rhijn, Ildiko; Van Berlo, Twan; Hilmenyuk, Tamara; Cheng, Tan Yun; Wolf, Benjamin J.; Tatituri, Raju V.V.; Uldrich, Adam P.; Napolitani, Giorgio; Cerundolo, Vincenzo; Altman, John D.; Willemsen, Peter; Huang, Shouxiong; Rossjohn, Jamie; Besra, Gurdyal S.; Brenner, M.B.; Godfrey, Dale I.; Moody, D.B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 2, 2016, p. 380-385.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Human autoreactive T cells recognize CD1b and phospholipids

AU - Van Rhijn, Ildiko

AU - Van Berlo, Twan

AU - Hilmenyuk, Tamara

AU - Cheng, Tan Yun

AU - Wolf, Benjamin J.

AU - Tatituri, Raju V.V.

AU - Uldrich, Adam P.

AU - Napolitani, Giorgio

AU - Cerundolo, Vincenzo

AU - Altman, John D.

AU - Willemsen, Peter

AU - Huang, Shouxiong

AU - Rossjohn, Jamie

AU - Besra, Gurdyal S.

AU - Brenner, M.B.

AU - Godfrey, Dale I.

AU - Moody, D.B.

PY - 2016

Y1 - 2016

N2 - In contrast with the common detection of T cells that recognize MHC, CD1a, CD1c, or CD1d proteins, CD1b autoreactive T cells have been difficult to isolate in humans. Here we report the development of polyvalent complexes of CD1b proteins and carbohydrate backbones (dextramers) and their use in identifying CD1b autoreactive T cells from human donors. Activation is mediated by αβ T-cell receptors (TCRs) binding to CD1b-phospholipid complexes, which is sufficient to activate autoreactive responses to CD1b-expressing cells. Using mass spectrometry and T-cell responses to scan through the major classes of phospholipids, we identified phosphatidylglycerol (PG) as the immunodominant lipid antigen. T cells did not discriminate the chemical differences that distinguish mammalian PG from bacterial PG. Whereas most models of T-cell recognition emphasize TCR discrimination of differing self and foreign structures, CD1b autoreactive T cells recognize lipids with dual self and foreign origin. PG is rare in the cellular membranes that carry CD1b proteins. However, bacteria and mitochondria are rich in PG, so these data point to a more general mechanism of immune detection of infection- or stressassociated lipids.

AB - In contrast with the common detection of T cells that recognize MHC, CD1a, CD1c, or CD1d proteins, CD1b autoreactive T cells have been difficult to isolate in humans. Here we report the development of polyvalent complexes of CD1b proteins and carbohydrate backbones (dextramers) and their use in identifying CD1b autoreactive T cells from human donors. Activation is mediated by αβ T-cell receptors (TCRs) binding to CD1b-phospholipid complexes, which is sufficient to activate autoreactive responses to CD1b-expressing cells. Using mass spectrometry and T-cell responses to scan through the major classes of phospholipids, we identified phosphatidylglycerol (PG) as the immunodominant lipid antigen. T cells did not discriminate the chemical differences that distinguish mammalian PG from bacterial PG. Whereas most models of T-cell recognition emphasize TCR discrimination of differing self and foreign structures, CD1b autoreactive T cells recognize lipids with dual self and foreign origin. PG is rare in the cellular membranes that carry CD1b proteins. However, bacteria and mitochondria are rich in PG, so these data point to a more general mechanism of immune detection of infection- or stressassociated lipids.

KW - CD1b

KW - Dendritic cell

KW - Lipid antigen

KW - Self-antigen

KW - T cell

U2 - 10.1073/pnas.1520947112

DO - 10.1073/pnas.1520947112

M3 - Article

VL - 113

SP - 380

EP - 385

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 - 2

ER -