The lack of a “chaperone” protein — called HLA-DO — that helps to protect the body against threats by presenting specific molecules (antigens) to immune cells to drive a response, promoted the development of a self-reactive immune system and autoimmune disease, according to a study in mice.
Particularly, the work showed that genetic deletion of HLA-DO resulted in a higher number of immune cells wrongly recognizing myelin (the protective coat of nerve cells) as a foreign antigen, and to a more severe disease in a mouse model of multiple sclerosis (MS).
“In our mouse study, we have shown that a specific disruption in this regimen [the normal processes of antigen presentation] can redirect the immune system to turn against a healthy body — something that we believe also is likely occurring in humans,” Scheherazade Sadegh-Nasseri, PhD, the study’s senior author and a professor of pathology at the Johns Hopkins University School of Medicine, said in a press release.
These findings, along with a previously reported association between HLA-DO genetic variants and autoimmune disease, highlight the usefulness of screening people for these variants to identify those at greater risk for these conditions, potentially allowing early interventions.
The study, “Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases,” was published in the journal PLOS Biology.
Self-tolerance, or the capacity of a person’s immune system to avoid attacking the body’s own cells and molecules, requires education of both T- and B-cells (two major types of immune cells). These cells have specific surface receptors to recognize foreign molecules.
B-cells and other immune cells can “ingest,” process, and present these antigens to T-cells, which are the main regulators of immune responses.
T-cells learn to discriminate “self” from “non-self” antigens in the thymus, a chest-located organ. A specialized subset of cells in the thymus, called medullary thymic cells, have the ability to present tissue-specific self-antigens to T-cells, and those with receptors that bind strongly to these antigens are selected for elimination.
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