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Human Leukocyte Antigen (HLA)

About || Types || Importance in Disease || Overview || Related Articles
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About





The human leukocyte antigen (HLA) is a set of genes located on chromosome 6. They encode protein molecules known as "major histocompatibility complexes" (MHC) that play a pivotal role in proper immune function.

Each human being inherits half of their HLA genes from their mother on one chromosome 6, and half from their father on their other chromosome 6. Because of this random mixing of HLA genes a greater diversity of immune responses is possible amongst the population, which ensures survival of the species.

Major histocompatibility complex proteins get embedded in the membranes of nearly every cell in the human body. From there the MHC proteins "display" various antigens to other cells in the body. The antigens can be protein fragments of viral, bacterial, or self origin depending on the type of MHC protein.

The combination of the MHC protein plus its antigen is able to bind to specific receptors on T-cells (another important immune related cell). The T-cell may then "rev" up the immune system to fight any detected abnormalities. In essence, the MHC proteins allow cells in the body to "talk" with the immune system, which allows them to tell the immune system what infections may be brewing.

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Types

There are two categories of human leukocyte antigen genes. Those that encode for MHC-1 proteins, and those that encode for MHC-2 proteins. The genes that encode for MHC-1 are given single letter names such as HLA-A, HLA-B, etc. The genes that encode for MHC-2 get two letter names such as HLA-DR, HLA-DQ, etc.

HLA genes encode
type 1 and type 2
MHC proteins
MHC-1 proteins display antigens (ie: protein fragments) that come from inside the cell. For example, viral proteins that are created inside a cell after it becomes infected would eventually get shown to T-cells by MHC-1 proteins on the cell's surface. The MHC-1 proteins are expressed on all nucleated cells in the body. They are a vital component of viral immunity.

MHC-2 proteins show antigen that originates from outside the cell. For example, some cells are able to gobble up bacteria and chew up its proteins. These cells are known as antigen presenting cells (APCs). They take that gobbled up bacterial protein and show it to T-cells on MHC-2 proteins embedded in their cellular membranes.

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HLA Genes and Disease

For complicated reasons specific HLA genes are linked to various autoimmune disorders. For example, the HLA-B8 gene (which encodes an MHC-1 protein) is associated with an increased risk of Grave's disease. HLA-DR4 is seen in higher frequencies in patient's with rheumatoid arthritis and diabetes mellitus type 1. See the table below for a more complete list of diseases associated with specific HLA genes.

HLA Gene Associated Disease
DR2

- Multiple sclerosis
- Goodpasture's disease
- Systemic lupus erythematosus

DR3

- Diabetes mellitus
- Systemic lupus erythematosus

DR4

- Rheumatoid arthritis
- Diabetes mellitus type 1
- Pemphigus vulgaris

DR5

- Pernicious anemia
- Hashimoto's thyroiditis

DQ3 - Alopecia areata
B8 - Grave's disease
- Systemic lupus erythematosus
B27

- Psoriasis
- Inflammatory bowel disease
- Ankylosing spondylitis

A3 - Hemochromatosis

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Overview

The human leukocyte antigens are a set of genes located on chromosome 6 that encode for major histocompatibility complex proteins. MHC proteins play a vital role in cellular immunity. For unclear reasons, certain HLA genes are associated with specific autoimmune disorders.

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Related Articles

- Lipoproteins

- Multiple sclerosis

- Diabetes mellitus

- Systemic lupus erythematosus

- Rheumatoid arthritis

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References and Resources

(1) Larsen CE, Alper CA. The genetics of HLA-associated disease. Current opinion in Immunology 2004, 16:660-667.

(2) Le T, Bhushan V, Grimm L. First Aid for the USMLE Step 1. New York: McGraw Hill, 2009.

(3) Harvey RA, Champe PC. Lippincott's Illustrated Reviews: Immunology (Lippincott's Illustrated Reviews Series). First Edition. Lippincott-Ravens Publishers, 2007.

(4) Hansen TH, Connolly JM, Gould KG, et al. Basic and translational applications of engineered MHC class I proteins. Trends Immunol. 2010 Oct;31(10):363-9. Epub 2010 Sep 9.

(5) Li XC, Raghavan M. Structure and function of major histocompatibility complex class I antigens. Curr Opin Organ Transplant. 2010 Aug;15(4):499-504.

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An antigen is a molecule (think along the lines of bacterial and viral proteins) that when introduced to the immune system triggers the formation of antibodies. Antibodies are proteins that neutralize antigens and prevent them from causing damage.