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Immune molecule that plays a powerful role in avoiding organ rejection identified
Date:6/16/2008

is dimer form is at work in kidney transplant patients who avoid rejection.

HLA-G dimer's target is another MHC molecule, which is essentially an individual's unique tissue signature; HLA-G itself is a type of MHC. In fact, HLA - human leukocyte antigen - matching is done for organ and bone marrow transplants to try minimize the recipient's reaction to the new organ. Transplant patients also take drugs that broadly dampen the immune response but can leave them more vulnerable to infections and disease.

Dr. Horuzsko notes that HLA-G can work through other cells, not just MHC molecules, and that not every HLA-G form is good at down-regulating MHC.

He plans to look at HLA-G dimer levels in tumor patients as well. "Tumors already down- regulate MHC molecules," he says, referencing how tumors turn down their tissue expression so they can fly below the radar of the immune system. "We need to see what form of HLA-G cancers - including leukemia, lymphoma, melanoma and breast cancer - use and see their level of expression." He notes that HLA-G isn't the only mechanism cancers use to escape the immune response but that being able to control a tumor's use of this molecule could offer a new way to target tumors for natural destruction.

A recent grant from the National Multiple Sclerosis Society is enabling studies of whether down-regulating MHC expression in multiple sclerosis patients can slow or arrest the immune system's attack of the nerve's protective covering. "The expression of the MHC molecule for some reason goes up - an infection might trigger the recognition of your own tissue - and the immune system attacks," says Dr. Horuzsko. "We can generate a mouse with MS-like disease and target the HLA-G inhibitory receptor to see if it effectively down-regulates the disease." He'll look to see which, if any, of the HLA-G forms are most powerful in this autoimmune scenario.


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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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