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Alternative splicing of MR1 regulates antigen presentation to MAIT cells

Gitanjali A Narayanan1, Abhinav Nellore1,2, Jessica Tran3

  • 1Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA.

Scientific Reports
|September 23, 2020
PubMed

Insights

Alternative splicing of the MR1 molecule regulates Mucosal Associated Invariant T (MAIT) cell activation. MR1B isoform expression inhibits MAIT cell responses, impacting immune surveillance of intracellular pathogens.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Mucosal Associated Invariant T (MAIT) cells are crucial for sensing intracellular infections.
  • MAIT cell activation depends on microbial antigens presented by the MR1 molecule.
  • Human MR1 exhibits alternative splicing, producing isoforms with distinct functions.

Purpose of the Study:

  • To characterize the expression and function of human MR1 splice variants (MR1A, MR1B, MR1C).
  • To investigate how MR1 isoforms regulate MAIT cell activation.
  • To explore the role of MR1 splicing in thymocyte development.

Main Methods:

  • Transcriptomic analysis
  • Quantitative Polymerase Chain Reaction (qPCR)
  • MAIT cell activation assays
  • Flow cytometry analysis of thymocytes

Main Results:

  • MR1A and MR1B transcripts are widely expressed, but only MR1A presents mycobacterial antigens to MAIT cells.
  • Coexpression of MR1B with MR1A reduces MAIT cell activation.
  • MR1B expression can decrease MR1A abundance, suggesting competition for ligands or chaperones.
  • The MR1A/MR1B transcript ratio correlates with MR1+CD4/CD8 thymocyte prevalence.

Conclusions:

  • Alternative splicing of MR1 is a regulatory mechanism for MAIT cell activation.
  • MR1B acts as a negative regulator of MAIT cell responses.
  • MR1 splicing influences immune cell development and function in the thymus.

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