The burgeoning family of unconventional T cells

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.

Mucosal‐associated invariant T cells in autoimmunity, immune‐mediated diseases and airways disease

“…This feature, alongside the striking evolutionary conservation of MR1 across over 150 million years of mammalian evolution,3, 92, 93, 94, 95 imply a strong evolutionary pressure maintaining the MAIT cell repertoire, and hence some indispensible role in host defence. This limited diversity of MAIT‐TCR, and the abundance of MAIT cells in humans means that, early in an immune response MAIT cells may markedly outnumber responses from conventional peptide‐specific αβ T cells 14. Abbreviations: MAIT , mucosal‐associated invariant T; MR 1, MHC‐related protein 1; TCR , T‐cell receptor; TRAV , TCR‐ α chain variable region; TRVB , TCR‐ β chain variable region.…”

“…MAIT cells display an intrinsic effector‐memory phenotype – i.e. without the need for prior clonal expansion14 – typically CD45RA − CD45RO + CD95 Hi CD62L Lo CD44 Hi 2, 15, 16, 17 – and can rapidly secrete a range of pro‐inflammatory cytokines including tissue necrosis factor‐ α (TNF‐ α ), interleukin‐17 (IL‐17) and interferon‐ γ (IFN‐ γ ), and also the type 2 cytokine IL‐4 on TCR ligation 15, 17. MAIT cells share some similarities with invariant natural killer T (iNKT) cells, which are implicated in many autoimmune conditions,18, 19 including expression of a semi‐invariant TCR, restriction by non‐classical MHC molecules, and expression of the transcription factor promyelocytic leukaemia zinc finger protein (PLZF)20 although many differences exist, notably the nature of the ligands and the restriction molecule.…”

“…A peculiarity of MAIT cell biology is that although MR1 expression is ubiquitous,3, 26 it is normally found only at very low levels on the cell surface 26, 27, 28. This has led to speculation that if other classes of MAIT cell ligand exist, they might include autologous molecules whose presentation at the cell surface occurs only when MR1 surface expression is up‐regulated as a signal of cell stress,2, 27, 29 as occurs with other class 1b molecules 14, 30. Inappropriate triggering of such a system would be expected to lead to immune pathology.…”

Structural determination of lipid antigens captured at the CD1d–T-cell receptor interface

“…However, certain subsets of human T cells, such as invariant natural killer T (iNKT) cells, mucosal-associated invariant T cells, and germline-encoded mycolylreactive T cells reliably generate T-cell receptors (TCRs) that are conserved among genetically diverse humans, and in some cases, across species (1). Recent data indicate that T cells expressing such invariant TCRs comprise a significant fraction of all human T cells, estimated in the range of 10-20% (2).…”

The Role of the Innate and Adaptive Immunity in Exercise Induced Muscle Damage and Repair

“…Immunologists now can separate ILCs more specifically with a range of cell surface markers, and therefore it may be important to reevaluate the responses of Group1 ILCs in response to exercise by flow cytometry. In addition to the ILC subsets other novel T cell derived innate repertoires including GEM T cells and MAIT T cells have been shown to response to microbial derived products in the context of non-classical MHC molecules [100]. Nothing is known about these new populations of innate T cells in the context of exercise or tissue repair.…”