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CD1a-autoreactive T cells are a normal component of the human αβ T cell repertoire

Nature Immunology volume 11, pages 1102–1109 (2010)Cite this article

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Abstract

CD1 activates T cells, but the function and size of the possible human T cell repertoires that recognize each of the CD1 antigen-presenting molecules remain unknown. Using an experimental system that bypasses major histocompatibility complex (MHC) restriction and the requirement for defined antigens, we show that polyclonal T cells responded at higher rates to cells expressing CD1a than to those expressing CD1b, CD1c or CD1d. Unlike the repertoire of invariant natural killer T (NKT) cells, the CD1a-autoreactive repertoire contained diverse T cell antigen receptors (TCRs). Functionally, many CD1a-autoreactive T cells homed to skin, where they produced interleukin 22 (IL-22) in response to CD1a on Langerhans cells. The strong and frequent responses among genetically diverse donors define CD1a-autoreactive cells as a normal part of the human T cell repertoire and CD1a as a target of the TH22 subset of helper T cells.

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Figure 1: Population study of CD1-autoreactive cells in blood of human donors.
Figure 2: Autoreactive T cells in the blood recognize CD1a.
Figure 3: Quantitative detection of CD1a-autoreactive memory T cells.
Figure 4: CD1a-autoreactive T cells in the blood express skin-homing markers.
Figure 5: CD1a-dependent IL-22 production.
Figure 6: The TH22 subset contains CD1a-autoreactive T cells.
Figure 7: IL-22 producing CD1a-autoreactive T cells in human skin.

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Acknowledgements

We thank D.C. Barral, M. Brenner and M. Relloso (Harvard Medical School) and M. Sugita (Kyoto University) for CD1 plasmid constructs; J. Gumperz (University of Wisconsin) and M. Brigl (Harvard Medical School) for human NKT cell lines; G. Losyev for cell sorting; and K. Magalhães, S. Huang, I.C. Ho and R. Grenningloh for technical advice. Supported by the National Institute of Arthritis, Musculoskeletal and Skin Diseases (048632 to D.B.M. and AR056720 to R.A.C.), the National Institute of Allergy and Infectious Diseases (AI071155 to D.B.M., and AI054456 and AI056299), the Damon Runyon Cancer Research Foundation (R.A.C.), the Burroughs Wellcome Fund (D.B.M.) and the National Psoriasis Foundation (A.d.J.).

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Authors and Affiliations

  1. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Annemieke de Jong, Tan-Yun Cheng, Ildiko Van Rhijn & D Branch Moody

  2. Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Victor Peña-Cruz

  3. Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Rachael A Clark

  4. Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

    Ildiko Van Rhijn

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  1. Annemieke de Jong
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  2. Victor Peña-Cruz
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  3. Tan-Yun Cheng
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  4. Rachael A Clark
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  5. Ildiko Van Rhijn
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Contributions

A.d.J. designed and did the experiments; A.d.J. and D.B.M. prepared the manuscript; D.B.M. supervised the experiments; V.P.-C. isolated LCs from human epidermis and lymphocytes from the dermis; T.-Y.C. did T cell culture and immunoblot analysis; I.V.R. assisted in experiments; and R.A.C. provided T cells isolated from human skin biopsies.

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Correspondence to D Branch Moody.

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de Jong, A., Peña-Cruz, V., Cheng, TY. et al. CD1a-autoreactive T cells are a normal component of the human αβ T cell repertoire. Nat Immunol 11, 1102–1109 (2010). https://doi.org/10.1038/ni.1956

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