Human Leukocyte Antigens and Autoimmunity: The Role of HLA markers in the Immune Response

Various protein antigenic molecules found on white blood cells determine what substances our immune system cells will react with and to what degree.

Various HLA markers highly influence the immune response. These markers are comprised of the class I and class II Human Leukocyte antigens (HLA). To date, 3,3731 different antigen alleles have been identified. The HLA type represents one’s HLA antigen profile just as the blood type represents the antigen markers on one’s red blood cells.

HLA antigens were first studied as a means of tissue typing compatible donors for transplant matching. Tissue donors with the same HLA profile as the recipient are likely to donate organs that aren’t rejected. Today, tests for HLA antigens are also used to understand patterns of autoimmunity, vaccine efficacy, and one’s response to therapeutic agents.

HLA Testing

Today, tests for HLA typing are also more sophisticated than the early tests, and they rely on DNA-based sequencing technologies rather than antigen-antibody reactions. With these technological advances, HLA testing is more specific and sensitive.

Class I and II HLA Antigens

Class I HLA molecules identify the internal contents of cells and display these contents on the cell surface. Class I molecules act as the cell’s internal alarm system, sounding an alert when changes suggest cancer or viral infections.

Class II HLA molecules act as an external alarm system, initiating an immune response when the body encounters extracellular microorganisms. These HLA antigens prompt the recruitment of antibodies and other immune system components that can fight and eliminate cancerous changes and infected cells. Everyone has their own unique HLA alarm system depending on their HLA type. Different HLA molecules typically send alarms in dissimilar ways.

For instance, the class I HLA antigen B5701 is thought to efficiently alert immune cells to the presence of the HIV virus. This antigen helps to control HIV infection. This is an example of how HLA typing can help identify host resistance or susceptibility to particular organisms as well as drug therapies.

When the HLA-directed immune response is working properly, it protects the body. However, if this immune response is too weak or too strong, it can lead to rheumatoid arthritis, transplant rejection, cancer and infection.


HLA typing has become increasingly important in the study of autoimmune diseases. It’s long been known that certain HLA antigens confer susceptibility to specific autoimmune diseases, and certain HLA antigens offer protection. For instance, a majority of (but not all) Caucasion patients with Graves’ disease have been found to have HLA B8 and HLA Dr3 but not HLA B7. HLA B8 and DR3 are associated with susceptibility to Graves’ disease and HLA B7 is thought to protect against the development of Graves’ disease. Genetic susceptibility can vary among different ethnic groups.

Because there are adequate diagnostic tests and procedures available for the diagnosis of most autoimmune diseases, HLA testing is not routinely performed. An exception is testing for HLA B27. This antigen is often seen in patients with ankylosing spondylitis, uveitis, seronegative spondyloarthropathies, and Reiter’s syndrome. Tests for HLA B27 are often used to help diagnose these conditions.

Adverse Drug Reactions

HLA typing is also useful in identifying the immune system’s response to various drugs. For instance, patients with HLA B1502 treated for seizure disorders with carbamazepine (Tegretol) have a high risk of developing Steven Johnson Disease. Patients infected with HIV who have HLA B5701 and a slower risk of disease progression are likely to react with hypersensitivity reactions to the antiviral drug Abacavir


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