Wednesday, August 12, 2020

A rare genetic mutation makes the MAIT cells vanish in the body, researchers find

A team of scientists from Monash Biomedicine Discovery Institute has found a rare genetic mutation in a patient that causes the MAIT cells to evade completely. They began the study with a patient suffering from a mild primary immunodeficiency, and the cause could not be identified. The patient was being treated by Dr. Samar Ojaimi in Australia, and his reports have been sent to a scientist at Australia National University to check for genetic analysis.

The researchers after analyzing the patient’s genome, have identified a homozygous mutation in a gene that encodes for a protein MR1. Major histocompatibility complex class 1-related gene protein (MR1) is a non-polymorphic, non-classical MHC class 1 protein, and it is composed of alpha-1,2,3 domains. Though other MHC molecules present peptides to CD4 or CD8 T cells to elicit an immune response, this MR1 class presents non-peptide material to a specialized set of T cells called MAIT cells.

MAIT ( Mucosal-associated invariant T cells) is a subset of T cells in the immune system that is mainly used for providing innate immunity response. They are usually found in blood, lungs, liver, mucosa. The MR1 molecule presents vitamin B antigen, produced by various bacterial species to the specific MAIT cells. MR1 molecules reside in the endoplasmic reticulum until the VitB antigen arrives and binds to it covalently, then further moves to the cell surface. After the presentation of foreign antigen by MR1, these MAIT cells secrete pro-inflammatory cytokines and are capable of killing infected bacterial cells.

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When the MR1 protein-producing gene is mutated, it prevents the binding of vitamin metabolite to MR1 protein, so that there would be a complete loss of the MAIT immune cell population. The study published in Science Immunology, reports that it was surprising to find that the MAIT cells are completely disappeared, while the rest of the immune system remain unaffected.

This kind of study is more useful in developing medicines for rare genetic and immune disorders. Genomics is indeed necessary to understand more about the immunological concept and assists us in both diagnosis and treatment of rare disease.

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Source: MedicalXpress

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