TY - JOUR T1 - Alternative Splicing of MR1 regulates antigen presentation to MAIT cells JF - bioRxiv DO - 10.1101/695296 SP - 695296 AU - Gitanjali A. Narayanan AU - Abhinav Nellore AU - Jessica G. Tran AU - Aneta H. Worley AU - Erin W. Meermeier AU - Elham Karamooz AU - Megan Huber AU - Regina Kurapova AU - Fikadu Tafesse AU - Melanie J. Harriff AU - David M. Lewinsohn Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/11/695296.abstract N2 - 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.Funding This work was supported by NIH T32HL083808 (EK, GAN, EM), VA Merit Award I01CX001562 (MJH), NIH R01AI29976 (MJH), NIH R01AI048090 (DML), NIH R21AI124225-01A1 (FT) and VA Merit Award I01BX000533 (DML). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. ER -