Tuesday, January 20, 2015

MAIT cells


In my opinion, Immunology is quite naive when compared to fields of microbiology, and the networks and components of the system is more complex. The players in immunology is often difficult in terms of understanding them, since many components have multiple functions. Some of the functions are contrast themselves and varies based on the context. When we talk about Immune cells, it is one among the following- Neutrophils, Monocytes, Eosinophils, Basophils and Lymphocytes. Among these, Lymphocytes represents structurally similar, collection of phenotypes.

Broadly stating the lymphocyte belongs to T cell or B cell category, and rest are called as "others". It has recently become clear that these "others", represent a huge number of varieties. T- cells in itself is a huge collection. I have previously blogged about a set called Helper cells which belongs to a subset of CD4+ T cells (Link).

Immune system is a learning based defense system. But to learn, the immune cells take sometime. The time lost in having to learn the defense is compensated by the innate defense system which is not so effective. Here is the interesting point. Researcher's are now slowly discovering a set of players that falls in a middle category. They are usually known as invariant cells. Probably the NK (Natural Killer) cells are more familiar to the reader in that category. But more recently I was introduced to another- MAIT cells, which is taking up a center stage in immunology field.

MAIT stands for "Mucosal associated invariant T cells". They form roughly 5% of cells of circulating T cells. They are characterized by the expression of a semi-invariant TCR (Vα7.2-Jα33/12/20) that recognizes the evolutionary conserved MHC-related protein 1 (MR-1), which is receptive for bacterial antigens. They express mainly CD161 and IL-18R. They maybe considered as a member of non-classical T cells. Their response is not determined by priming and hence you may consider it as innate cell. This means they have a ability to respond to a wide variety of pathogens from Mycobacterium to Candida species.

Fig 1: MAIT cells.
The mystery of how can a receptor recognize a broad range was solved by studying the structural aspects of MR-1. It showed that MR-1 basically recognizes microbial metabolites of riboflavin. These metabolites (for example reduced 6-hydroxymethyl-8-D-ribityllumazine, 7-hydroxy-6-methyl-8-D-ribityllumazine and its precursor, 6,7-dimethyl-8-D-ribityllumazine) are potential MAIT-activating ligands. To put in a simple language, the MAIT cells are recognizing a totally new set of antigens which can be sensed very early. Remember Vitamin components are widely available in mucosal regions and their microbial metabolites is a very good candidate for immune system to survey in mucosal context.

The interest in MAIT cells comes from a variety of angles. From the point of basic Immunobiology, MAIT cells were not observed in germ-free mice or in germ-free mice repopulated with bacteria's. They secrete IL-17 which can stimulate Th17 cells, known players of antibacterial immunity. Interestingly, MAIT cells is not a homogenous variety. It comes in CD4+ and CD8+ varieties. Further, MAIT cells require B cells as well as commensal flora for their peripheral expansion. From a clinical perspective, MAIT cells is thought to play a protective role in Multiple sclerosis and a pathogenic role in arthritis. Mucosal immunity is an important emerging area of understanding HIV pathogenesis. There is a consistent evidence of MAIT cell depletion in HIV cases.

MAIT cells have just begun to be understood, and probably is inclusive of multiple sub immunotypes. The biology would be interesting to studied in further detail

Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O'Hair RA, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, & McCluskey J (2012). MR1 presents microbial vitamin B metabolites to MAIT cells. Nature, 491 (7426), 717-23 PMID: 23051753

Leeansyah E, Ganesh A, Quigley MF, Sönnerborg A, Andersson J, Hunt PW, Somsouk M, Deeks SG, Martin JN, Moll M, Shacklett BL, & Sandberg JK (2013). Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. Blood, 121 (7), 1124-35 PMID: 23243281

Ussher JE, Klenerman P, & Willberg CB (2014). Mucosal-associated invariant T-cells: new players in anti-bacterial immunity. Frontiers in immunology, 5 PMID: 25339949

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