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 incompletely understood. In this report, we sought to characterize the expression and function of these splice variants. Using a transcriptomic analysis in conjunction with qPCR, we find that that MR1A and MR1B transcripts are widely expressed. However only MR1A can present mycobacterial antigen to MAIT cells. Coexpression of MR1B with MR1A decreases MAIT cell activation following bacterial infection. Additionally, 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. Here, we find that relative expression of MR1A/MR1B transcript is associated with the prevalence of MR1 + CD4/CD8 cells in the thymus. Our results suggest alternative splicing of MR1 represents a means of regulating MAIT activation in response to microbial ligand(s).

粘膜相关不变 T (MAIT) 细胞可以感知多种病原体的细胞内感染。这些细胞在遇到 MR1 在受感染细胞表面展示的微生物抗原时被激活。人类 MR1 经历选择性剪接。全长同种型 MR1A 可以激活 MAIT 细胞，而同种型 MR1B 和 MR1C 的功能尚不完全清楚。在本报告中，我们试图表征这些剪接变体的表达和功能。将转录组学分析与 qPCR 结合使用，我们发现 MR1A 和 MR1B 转录物被广泛表达。然而，只有 MR1A 可以将分枝杆菌抗原呈递给 MAIT 细胞。MR1B 与 MR1A 的共表达会降低细菌感染后的 MAIT 细胞活化。此外，在 MR1A 之前表达 MR1B 会降低总 MR1A 丰度，表明 MR1A 和 MR1B 之间竞争折叠和/或运输所需的配体或分子伴侣。最后，我们评估了表达表面 MR1 的 CD4/CD8 双阳性胸腺细胞。在这里，我们发现相对表达MR1A/MR1B转录本与胸腺中 MR1 + CD4/CD8 细胞的流行有关。我们的结果表明，MR1 的选择性剪接代表了一种调节 MAIT 激活以响应微生物配体的手段。