Alternative Splicing of MR1 regulates antigen presentation to MAIT cells
release_rev_19c912cb-da16-41b5-868a-82e19798ef1f
by
Gitanjali A Narayanan, Abhinav Nellore, Jessica Tran, Aneta H Worley, Erin W Meermeier, Elham Karamooz, Megan Huber, Regina Kurapova, Fikadu Tafesse, Melanie J Harriff, David M Lewinsohn
2019
Abstract
Mucosal Associated Invariant T (MAIT) cells can sense intracellular infection by a broad array of pathogens. These cells are activated upon encountering microbial antigen(s) displayed by MR1 on the surface of an infected cell. Human MR1 undergoes alternative splicing. The full length isoform, MR1A, can activate MAIT cells, while the function of the isoforms, MR1B and MR1C, are not well characterized. In this report, we sought to characterize these splice variants. Using a transcriptomic analysis in conjunction with qPCR, we find that that MR1A and MR1B transcripts are widely expressed. Despite the widespread expression of MR1A and MR1B, only MR1A can present mycobacterial antigen to MAIT cells. Coexpression of MR1B with MR1A serves to decrease MAIT cell activation following bacterial infection. However, expression of MR1B prior to MR1A lowers total MR1A abundance, suggesting competition between MR1A and MR1B for either ligands or chaperones required for folding and/or trafficking. Finally, we evaluated CD4/CD8 double positive thymocytes expressing surface MR1. Relative MR1A/MR1B expression in MR1-expressing thymocytes is associated with their prevalence. Our results suggest alternative splicing of MR1 represents a means of regulating MAIT activation in response to microbial ligand.
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Date 2019-07-11
10.1101/695296
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