Human Leukocyte Antigen (HLA): Definition & Testing

Instructor: Danielle Haak

Danielle has a PhD in Natural Resource Sciences and a MSc in Biological Sciences

Human leukocyte antigens (HLA) are cellular proteins that can trigger an immune system response. Each person has a unique HLA complex, so matching potential organ donors and recipients requires testing and comparing each person's HLA complex.

What Is Human Leukocyte Antigen (HLA)?

The body's immune system is the primary defense mechanism we have against getting sick, but how do the immune system's cells know which cells are friendly and which are potential enemies?

Each cell in the body displays a unique set of protein markers (or identifying molecules) decided by our genetic makeup. It's kind of like if all of our cells carried a specific flag with the logo of your body. If a cell with a different flag comes along, the immune system will see that's it's an invader.

All animals carry a set of genes that code for these proteins, called the major histocompatibility complex (MHC). Humans have a set of these genes too, their group is called the human leukocyte antigen (HLA).

HLA is therefore a gene complex responsible for deciding what markers (flags) display on the cells, but also refers to the proteins themselves. The immune system can check each marker to determine which cells are supposed to be there and which ones are invaders.


An antigen is any particle that triggers a response from the immune system, so if an invader cell is identified, the immune system begins making antibodies to attack and destroy it.

Because each person's HLA complex is relatively unique, the MHC proteins are different for each person. This means one person's cells aren't compatible with everyone else's. This becomes especially important when a person gets sick and needs a bone marrow or organ transplant.

HLA Classes

The antigens of the HLA complex can be categorized into three classes: Class 1, Class 2, and Class 3.

Generally speaking, when comparing HLA complexes, 6-10 different markers are identified, and these are all found in Classes 1 or 2.

  • In Class 1, the HLA-A, HLA-B, and HLA-C markers are compared.
  • In Class 2, the HLA-DRB1 and HLA-DQ markers are compared.

There are two of each, so a 'perfect match' would be a 10 out of 10. Most transplants require at least 6 matching markers (though more are better).

A person's HLA complex is genetically inherited from their parents (50% from each parent), so you are more likely to have stronger matches with your siblings than with a random member of the population; however, each pair of siblings still only has a 25% chance of matching perfectly. The likelihood of having a perfect match with someone unrelated to you is approximately 1 in 100,000.

Specific information on the HLA complex are found on chromosome 6 in humans.
HLA Complex

Say that Rich is a patient who needs a bone marrow transplant. Doctors might test his brother Jeremy's HLA complex to see if they are a match and if Jeremy can be a bone marrow donor. If the donor (Jeremy) and recipient (Rich) have dramatically different HLA complexes, their MHC proteins are different, and Rich's immune system's cells will likely (though not always) attack and kill Jeremy's cells and reject the transplant.

In other words, the closer the match between two people, the less likely the recipient's immune system will attack the donor's cells. Let's look into this testing more.

HLA Testing

The HLA classes are important when we need to compare HLA complexes of two (or more) people through a histocompatibility antigen test (this is sometimes also called typing). The test involves analyzing the blood cells to look for specific proteins or antigens.

'Histo-' is Greek for 'tissue', so when you see the word 'histocompatibility' you can know that some kinds of tissue are being compared to see if they are compatible. In this case, that tissue is antigens on cells.

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