CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens

Dalam Ly, Anne G. Kasmar, Tan Yun Cheng, Annemieke de Jong, Shouxiong Huang, Sobhan Roy, Apoorva Bhatt, Ruben P. van Summeren, John D. Altman, William R. Jacobs, Erin J. Adams, Adriaan J. Minnaard, Steven A. Porcelli, D. Branch Moody

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

CD1c is expressed with high density on human dendritic cells (DCs) and B cells, yet its antigen presentation functions are the least well understood among CD1 family members. Using a CD1c-reactive T cell line (DN6) to complete an organism-wide survey of M. tuberculosis lipids, we identified C32 phosphomycoketide (PM) as a previously unknown molecule and a CD1c-presented antigen. CD1c binding and presentation of mycoketide antigens absolutely required the unusual, mycobacteria-specific lipid branching patterns introduced by polyketide synthase 12 (pks12). Unexpectedly, one TCR responded to diversely glycosylated and unglycosylated forms of mycoketide when presented by DCs and B cells. Yet cell-free systems showed that recognition was mediated only by the deglycosylated phosphoantigen. These studies identify antigen processing of a natural bacterial antigen in the human CD1c system, indicating that cells act on glycolipids to generate a highly simplified neoepitope composed of a sugar-free phosphate anion. Using knowledge of this processed antigen, we generated human CD1c tetramers, and demonstrate that CD1c-PM complexes stain T cell receptors (TCRs), providing direct evidence for a ternary interaction among CD1c-lipid-TCR. Furthermore, PM-loaded CD1c tetramers detect fresh human T cells from peripheral blood, demonstrating a polyclonal response to PM antigens in humans ex vivo.

Original languageEnglish (US)
Pages (from-to)729-741
Number of pages13
JournalJournal of Experimental Medicine
Volume210
Issue number4
DOIs
StatePublished - 2013

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Antigen Presentation
T-Cell Antigen Receptor
T-Lymphocytes
Antigens
Lipids
Dendritic Cells
B-Lymphocytes
Sugar Phosphates
Polyketide Synthases
Bacterial Antigens
Cell-Free System
Glycolipids
Mycobacterium
Anions
Tuberculosis
Coloring Agents
Cell Line

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Ly, D., Kasmar, A. G., Cheng, T. Y., de Jong, A., Huang, S., Roy, S., ... Moody, D. B. (2013). CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. Journal of Experimental Medicine, 210(4), 729-741. https://doi.org/10.1084/jem.20120624

CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. / Ly, Dalam; Kasmar, Anne G.; Cheng, Tan Yun; de Jong, Annemieke; Huang, Shouxiong; Roy, Sobhan; Bhatt, Apoorva; van Summeren, Ruben P.; Altman, John D.; Jacobs, William R.; Adams, Erin J.; Minnaard, Adriaan J.; Porcelli, Steven A.; Moody, D. Branch.

In: Journal of Experimental Medicine, Vol. 210, No. 4, 2013, p. 729-741.

Research output: Contribution to journalArticle

Ly, D, Kasmar, AG, Cheng, TY, de Jong, A, Huang, S, Roy, S, Bhatt, A, van Summeren, RP, Altman, JD, Jacobs, WR, Adams, EJ, Minnaard, AJ, Porcelli, SA & Moody, DB 2013, 'CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens', Journal of Experimental Medicine, vol. 210, no. 4, pp. 729-741. https://doi.org/10.1084/jem.20120624
Ly, Dalam ; Kasmar, Anne G. ; Cheng, Tan Yun ; de Jong, Annemieke ; Huang, Shouxiong ; Roy, Sobhan ; Bhatt, Apoorva ; van Summeren, Ruben P. ; Altman, John D. ; Jacobs, William R. ; Adams, Erin J. ; Minnaard, Adriaan J. ; Porcelli, Steven A. ; Moody, D. Branch. / CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. In: Journal of Experimental Medicine. 2013 ; Vol. 210, No. 4. pp. 729-741.
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AU - Huang, Shouxiong

AU - Roy, Sobhan

AU - Bhatt, Apoorva

AU - van Summeren, Ruben P.

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AU - Porcelli, Steven A.

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