Biased MAIT TCR Usage Poised for Limited Antigen Diversity?

Souter, Michael N T; Eckle, Sidonia B G

doi:10.3389/fimmu.2020.01845

Cited by 13 publications

(14 citation statements)

References 101 publications

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“…The non-canonical TCR rearrangements were highly diverse, with no CDR3 sequences shared between all four donors ( Supplementary Data 1 ). The non-canonical TCR may be the result of nonspecific binding of tetramer to non-MAIT cells, sorting impurities or non-MAIT cell MR1 reactive T cells, which are rare populations identified in mice and humans ( 58 ). TRAV1 - TRAJ33 + cattle MAIT TCRs featured two similar CDR3 sequences, the predominant sequence of which was CVV M DGNYQWIW with a secondary sequence observed in all animals with a single aa substitution of methionine to isoleucine at position 91 ( Figure 4D and Supplementary Data 1 ).…”

Section: Resultsmentioning

confidence: 99%

Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections

et al. 2021

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Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells that utilize a semi-invariant T cell receptor (TCR) α chain and are restricted by the highly conserved antigen presenting molecule MR1. MR1 presents microbial riboflavin biosynthesis derived metabolites produced by bacteria and fungi. Consistent with their ability to sense ligands derived from bacterial sources, MAIT cells have been associated with the immune response to a variety of bacterial infections, such as Mycobacterium spp., Salmonella spp. and Escherichia coli. To date, MAIT cells have been studied in humans, non-human primates and mice. However, they have only been putatively identified in cattle by PCR based methods; no phenotypic or functional analyses have been performed. Here, we identified a MAIT cell population in cattle utilizing MR1 tetramers and high-throughput TCR sequencing. Phenotypic analysis of cattle MAIT cells revealed features highly analogous to those of MAIT cells in humans and mice, including expression of an orthologous TRAV1-TRAJ33 TCR α chain, an effector memory phenotype irrespective of tissue localization, and expression of the transcription factors PLZF and EOMES. We determined the frequency of MAIT cells in peripheral blood and multiple tissues, finding that cattle MAIT cells are enriched in mucosal tissues as well as in the mesenteric lymph node. Cattle MAIT cells were responsive to stimulation by 5-OP-RU and riboflavin biosynthesis competent bacteria in vitro. Furthermore, MAIT cells in milk increased in frequency in cows with mastitis. Following challenge with virulent Mycobacterium bovis, a causative agent of bovine tuberculosis and a zoonosis, peripheral blood MAIT cells expressed higher levels of perforin. Thus, MAIT cells are implicated in the immune response to two major bacterial infections in cattle. These data suggest that MAIT cells are functionally highly conserved and that cattle are an excellent large animal model to study the role of MAIT cells in important zoonotic infections.

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Section: Resultsmentioning

confidence: 99%

Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections

et al. 2021

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“…Once bound, MR1-metabolite complexes are displayed at the cell surface for recognition by innate-like MR1-restricted T (MR1-T) cells of which the most numerous are mucosal associated invariant T (MAIT) cells. MAIT cells express a semi-invariant αβ T cell receptor that recognises MR1 presenting riboflavin-derived microbial antigen, whereas other MR1-T cells are less abundant and express more diverse T cell receptors that recognise MR1 alone, or MR1 presenting other classes of antigens (as recently reviewed by Souter and Eckle (2020)). Compared to the almost infinite range of peptide antigens presented by MHC molecules, MR1 is known to bind a more limited number of metabolites, although the list of bona fide MR1 ligands is increasing (McWilliam and Villadangos, 2018).…”

Section: Introductionmentioning

confidence: 99%

Understanding and modulating the MR1 metabolite antigen presentation pathway

McWilliam

Salio

2021

Molecular Immunology

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“…The non-canonical TCR rearrangements were highly diverse, with no CDR3 sequences shared between all four donors ( Supplementary Data 1 ). The non-canonical TCR may be the result of nonspecific binding of tetramer to non-MAIT cells, sorting impurities or non-MAIT cell MR1 reactive T cells, which are rare populations identified in mice and humans (59). TRAV1 - TRAJ33 + cattle MAIT TCRs featured two similar CDR3 sequences, the predominant sequence of which was CVVMDGNYQWIW with a secondary sequence observed in all animals with a single aa substitution of methionine to isoleucine at position 91 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification and phenotype of MAIT cells in cattle and their response to bacterial infections

Edmans

Connelley

Jayaraman

et al. 2020

Preprint

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Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells that utilise a semi-invariant T cell receptor (TCR) α chain and are restricted by the highly conserved antigen presenting molecule MR1. MR1 presents microbial riboflavin biosynthesis derived metabolites produced by bacteria and fungi. Consistent with their ability to sense ligands derived from bacterial sources, MAIT cells have been associated with the immune response to a variety of bacterial infections, such as Mycobacterium spp., Salmonella spp. and Escherichia coli. To date, MAIT cells have been studied in humans, non-human primates and mice. However, they have only been putatively identified in cattle by PCR based methods; no phenotypic or functional analyses have been performed. Here, we identified a MAIT cell population in cattle utilising MR1 tetramers and high-throughput TCR sequencing. Phenotypic analysis of cattle MAIT cells revealed features highly analogous to those of MAIT cells in humans and mice, including expression of an orthologous TRAV1-TRAJ33 TCR α chain, an effector memory phenotype irrespective of tissue localisation, and expression of the transcription factors PLZF and EOMES. We determined the frequency of MAIT cells in peripheral blood and multiple tissues, finding that cattle MAIT cells are enriched in mucosal tissues as well as in the mesenteric lymph node. Cattle MAIT cells were responsive to stimulation by 5-OP-RU and riboflavin biosynthesis competent bacteria in vitro. Furthermore, MAIT cells in milk increased in frequency in cows with mastitis. Following challenge with virulent Mycobacterium bovis, a causative agent of bovine tuberculosis and a zoonosis, peripheral blood MAIT cells expressed higher levels of perforin. Thus MAIT cells are implicated in the immune response to two major bacterial infections in cattle. These data suggest that MAIT cells are functionally highly conserved and that cattle are an excellent large animal model to study the role of MAIT cells in important zoonotic infections.

show abstract

Biased MAIT TCR Usage Poised for Limited Antigen Diversity?

Cited by 13 publications

References 101 publications

Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections

Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections

Understanding and modulating the MR1 metabolite antigen presentation pathway

Identification and phenotype of MAIT cells in cattle and their response to bacterial infections

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