Mucosal associated invariant T cells: Don't forget your vitamins

Young, Mary; Gapin, Laurent

doi:10.1038/cr.2012.168

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…3, A and C). This is consistent with mutagenesis and structural studies of the human MAIT TCR showing that the residues critical to MR1-mediated recognition were largely confined to the MAIT TCR α-chain and CDR3β loop of the MAIT TCR β-chain (Reantragoon et al, 2012; Patel et al, 2013; Young and Gapin, 2013). Interestingly, although sampled from a more limited number of cells, the TRBV usage in the noncanonical TRAJ20 + and TRAJ12 + MAIT cells was dominated by TRBV6-4 genes (P < 0.0001 for TRAJ12 and P < 0.0001 for TRAJ20, Fisher’s exact test), suggesting preferential pairing of these TCRs may be associated with noncanonical MAIT cell development (Fig.…”

Section: Resultssupporting

confidence: 88%

“…Although the sequences of TRAJ33, TRAJ20, and TRAJ12 differ slightly, they are relatively conserved overall, and notably, all three gene segments contained the conserved Tyr95α residue within the CDR3α loop (Fig. 3 B), which was previously shown to be crucial for MAIT cell activation (Reantragoon et al, 2012; Patel et al, 2013; Young and Gapin, 2013). A single TRAV1-2 + TRAJ4 + TRBV6-4 + clone was also identified within the TRAV1-2 + CD161 hi fraction, but this lacked Tyr95α, making it less likely to be a MAIT cell.…”

Section: Resultsmentioning

confidence: 94%

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Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells

Reantragoon

Corbett

Sakala

et al. 2013

Journal of Experimental Medicine

525

787

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 94%

Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells

Reantragoon

Corbett

Sakala

et al. 2013

Journal of Experimental Medicine

525

787

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“…The protein is also involved in the development and expansion of a small population of T-cells expressing an invariant T-cell receptor alpha chain called mucosal-associated invariant T-cells (42,43). Mucosal-associated invariant T-cells lymphocytes are preferentially located in the gut lamina propria and therefore may be involved in monitoring commensal flora or serve as a distress signal (44,45). These findings may point to novel pathways associated with genetic variation that may potentially modify the effect of environmental factors (gut commensal bacterial and B vitamins) on risk of IBD and CRC (46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

751 Identification of a Common Variant With Potential Pleiotropic Effect on Risk of Inflammatory Bowel Disease and Colorectal Cancer

Khalili¹,

Brenner²,

Austin³

et al. 2013

Gastroenterology

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Although genome-wide association studies (GWAS) have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies. Among 11 794 CRC cases and 14 190 controls, rs11676348, the susceptibility single nucleotide polymorphism (SNP) for UC, was significantly associated with reduced risk of CRC (P = 7E−05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI 0.89-0.96). The association of the SNP with risk of CRC differed according to mucinous histological features (P heterogeneity = 0.008). In addition, the (T) allele was associated with lower risk of tumors with Crohn's-like reaction but not tumors without such immune infiltrate (P heterogeneity = 0.02) and microsatellite instability-high (MSI-high) but not microsatellite stable or MSI-low tumors (P heterogeneity = 0.03). The minor allele (T) in SNP rs11676348, located downstream from CXCR2 that has been implicated in CRC progression, is associated with a lower risk of CRC, particularly tumors with a mucinous component, Crohn's-like reaction and MSI-high. Our findings offer the promise of risk stratification of inflammatory bowel disease patients for complications such as CRC.

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