Role of the HLA Complex in Disease Susceptibility & Tissue Transplant

Instructor: Heather Adewale

Heather has taught reproductive biology and has researched neuro, repro and endocrinology. She has a PhD in Zoology/Biology.

Have you ever wondered why it is so hard to find the right match for someone who needs a new organ? Well it all comes down to these little protein markers, kind of like ID tags. This is the role of Human Leukocyte Antigen, or HLA for short.

I.D. Tags

Imagine a soccer game where all the players wore the same uniform. It would be kind of difficult to know who to pass to right? Or a war where both sides looked the same, how would you know your fellow soldiers from enemy soldiers? You need an identification system to help sort out who is who. That is the job of the human leukocyte antigen (HLA), a group of proteins located on the surface on immune and other tissue cells that act as ID badges for your body. They are the human version of the MHC or major histocompatabiliity complex. They identify the cells in your body as 'your cells'.

Why is this necessary? Well, the role of your immune system is to protect you from foreign invaders. Foreign cells that don't belong will have their own ID tags. The body needs to be able to differentiate between yours (self) and not yours (non-self); that is where HLA comes in. Cells with your personal HLAs are safe from your immune system. They help the body determine which cells belong and which don't.

Many foreign cells have their own proteins on their surface. These proteins often stimulate an immune response. Any protein or cell that stimulates a response from the immune system is called an antigen. Your HLA molecules are also considered antigens because if put into a foreign body, they will provoke an immune response and that body will attack them. This is why organ transplants are so difficult.

Tissue Transplants

There are many types of HLAs, but the three main types important for tissue transplants are HLA-A, HLA-B, and HLA-DR. Within each of these types there are multiple subtypes, for example HLA-B includes B1 - B118, and so on. Like dogs, they are all the same species, but you have many different breeds. All are different in their own way, but also the same.

What determines which types of HLAs you have? It's all in the genes! HLAs are inherited as a set; you get one of each HLA type from your mother and one of each from your father.

If you happen to need an organ transplant, it is important that the HLAs of the donor organ match as closely as possible to your own. If the donor's HLAs don't match, the body will see the organ as foreign and attack it. Since siblings have the same parents, an individual's best chance for a HLA match is a sibling and then a parent. Not only do HLA's need to match, but both the recipient and donor need to have compatible blood types.

That's not all! The recipient of the new organ cannot have antibodies to the HLAs of the donor organ.

Antibodies are proteins made by immune cells. Antibodies against a certain HLA subtype will attack cells with that HLA. Now remember, you have multiple types HLAs in your body. Sometimes people also have antibodies to certain types of HLAs. If these antibodies only react to a few of the HLA proteins, say 10% of the total HLAs on the donor organ, then it wouldn't pose as much of a problem as antibodies that reacted to 75% of the HLAs on the donor organ.

Now it may sound confusing, because we normally think of the term 'anti' as being against something, but in this case the antibodies are protecting you. However, if you focus on the term 'body' you can think of them as being against bodies (cells) that don't belong. They are like little foot soldiers attacking the invaders. They help out our immune system by attacking foreign cells. So if your antibodies are attacking the HLA cells of donated tissue, it is because they see that tissue as foreign. Really they are just trying to protect you.

Disease Susceptibility

Research linking HLAs to certain diseases is still ongoing. However, scientists think that certain HLAs may be involved in both autoimmune and infectious diseases like malaria, tuberculosis, and even cancer.

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