J Rheum Dis.  2015 Dec;22(6):337-345. 10.4078/jrd.2015.22.6.337.

Mucosal-associated Invariant T cells: A New Player in Innate Immunity

• Park YW
• Kee SJ

• KMID: 2222807
• DOI: http://doi.org/10.4078/jrd.2015.22.6.337

Abstract

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved T cells that are restricted by the non-classical major histocompatibility complex class-1b molecule MR1. MAIT cells recognize riboflavin (vitamin B2) derivatives in a MR1-dependent manner. Following antigen recongnition, MAIT cells rapidly produce Th1/Th17 cytokines, such as interferon-gamma and interleukin-17, in an innate-like manner. MAIT cells maintain an activated phenotype throughout the course of an infection, secrete inflammatory cytokines, and have the potential to directly kill infected cells, thus, playing an important role in controlling the host response. In this review, we discuss current knowledge regarding the role of MAIT cells in infectious diseases, cancers, and autoimmune diseases.

Keyword

Autoimmune diseases; Cytokine; MR1; Mucosal-associated invariant T cell; Vitamin B2

MeSH Terms

Autoimmune Diseases
Communicable Diseases
Cytokines
Immunity, Innate*
Interferon-gamma
Interleukin-17
Major Histocompatibility Complex
Phenotype
Riboflavin
T-Lymphocytes*
Cytokines
Interferon-gamma
Interleukin-17
Riboflavin

Figure

• 

  Figure 1. A schematic of key differences among conventional T cells, invariant natural killer T (iNKT) cells, and mucosal-associated invariant T (MAIT) cells in humans. In contrast to conventional adaptive T cells expressing both diverse T cell receptor (TCR) Vα and Vβ chains, MAIT cells and iNKT cells constitute two major subsets of innate-like T cells with semi-invariant TCR repertoires using TCR Vα7.2-Jα33 chains expressed together with selected TCR β chains and TCR Vα24-Jα33 chains paired with TCR Vβ11 chains, respectively. In addition, MAIT cells are characterized by a high expression of CD161 and interleukin-18Rα (IL-18Rα). MAIT cells and NKT cells recognize vitamin B2 metabolite antigens (Ag) and glycolipid Ag presented by the invariant major histocompatibility complex (MHC)-related 1 (MR1) molecule and MHC class 1-like CD1d molecule, respectively, which are both expressed on Ag-presenting cells. Upon Ag recognition, these innate-like T cells rapidly produce cytokines.

• 

  Figure 2. Mechanisms of mucosal-associated invariant T (MAIT) cell activation in human diseases. (A) Microbial infection. Bacteria or yeast stimulate MAIT cells in an MR1-dependent manner. MAIT cells are activated through Vα7.2-bearing MAIT cell T cell receptor (TCR) recognition of microbial-derived vitamin B metabolite antigens presented by MR1 on infected antigen-presenting cells (APCs). Upon infection, MAIT cells are activated by stimulation with interleukin (IL)-12 and IL-18 produced by APCs in an MR1-independent manner. Furthermore, activation of MAIT cells can be enhanced by other stimuli, such as IL-7 secreted by hep-atocytes in synergy with TCR stimulation. Activated MAIT cells produce Th1 cytokines (interferon [IFN]-γ and tumor necrosis factor [TNF]-α) and Th17 cytokines (IL-17 and IL-22) and directly release perforin and granzyme B, which are cytotoxic effector molecules, to kill infected cells. (B) Viral infection. Viruses stimulate MAIT cells in an MR1-independent manner. Virus-infected cells are activated by detection of their molecular patterns by pattern recognition receptors, such as ssRNA by TLR8, resulting in IL-12 and IL-18 production. (C) Autoimmune disease. MAIT cells are stimulated by IL-12 and IL-18 produced by pathologically activated inflammatory cells present in autoimmune diseases. Figure adapted from an original drawing by Howson et al. (Front Immunol 2015;6:303) [2].

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