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The burgeoning family of unconventional T cells

Nature Immunology volume 16, pages 1114–1123 (2015)Cite this article

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A Corrigendum to this article was published on 22 March 2016

A Corrigendum to this article was published on 19 January 2016

This article has been updated

Abstract

While most studies of T lymphocytes have focused on T cells reactive to complexes of peptide and major histocompatibility complex (MHC) proteins, many other types of T cells do not fit this paradigm. These include CD1-restricted T cells, MR1-restricted mucosal associated invariant T cells (MAIT cells), MHC class Ib–reactive T cells, and γδ T cells. Collectively, these T cells are considered 'unconventional', in part because they can recognize lipids, small-molecule metabolites and specially modified peptides. Unlike MHC-reactive T cells, these apparently disparate T cell types generally show simplified patterns of T cell antigen receptor (TCR) expression, rapid effector responses and 'public' antigen specificities. Here we review evidence showing that unconventional T cells are an abundant component of the human immune system and discuss the immunotherapeutic potential of these cells and their antigenic targets.

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Figure 1: Comparison of unconventional and MHC-restricted T cell responses.
Figure 2: Unconventional αβ T cell populations.
Figure 3: Populations of γδ T cells.
Figure 4: Frequency of some antigen-specific T cell types.
Figure 5: Antigens detected by unconventional αβ T cells.

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Change history

  • 13 November 2015

    In the version of this article initially published, the vertical axes of Figure 4 were labeled incorrectly as "(per 1 × 105 T cells)." The correct label is "(per 1 × 106 T cells)." These errors have been corrected for the PDF and HTML versions of this article.

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Acknowledgements

We thank M. Sugita and N. LaGruta for discussions. Supported by the National Health and Medical Research Council of Australia (1013667 and 1063587; 1020770 to D.I.G.; and AF50 to J.R.), the Australian Research Council (CE140100011 and LE110100106; and FT140100278 to A.P.U.), Cancer Council Victoria, the Bill and Melinda Gates Foundation Vaccine Accelerator, and the National Institute of Allergy and Infectious Diseases (AI049313, AR048632 and U19111224).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia

    Dale I Godfrey, Adam P Uldrich & James McCluskey

  2. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Parkville, Australia

    Dale I Godfrey & Adam P Uldrich

  3. Infection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia

    Jamie Rossjohn

  4. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK

    Jamie Rossjohn

  5. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia

    Jamie Rossjohn

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

    D Branch Moody

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  1. Dale I Godfrey
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Correspondence to Dale I Godfrey.

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D.I.G. is chair of the scientific advisory panel for Avalia Immunotherapies.

Supplementary information

Supplementary Table 1

Characteristics of non-conventional T cells (PDF 43 kb)

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Godfrey, D., Uldrich, A., McCluskey, J. et al. The burgeoning family of unconventional T cells. Nat Immunol 16, 1114–1123 (2015). https://doi.org/10.1038/ni.3298

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