Human leukocyte antigen
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The human leukocyte antigen system (HLA) is the group of genes in the human major histocompatibility complex (MHC) that encodes the cell-surface antigen-presenting proteins. These proteins are sometimes designated the Mhc, although this convention is not consistently observed.
Classification of HLAs
"HLA" is used in conjunction with a letter and number (e.g. HLA-B27) to designate a specific allele at a given HLA locus. The most intensely studied HLA genes are the nine so-called classical Mhc genes: HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1. HLAs can be further classified into class I MHC and class II MHC.
Besides functional HLA antigens, there are two additional HLA antigens in humans, HLA-DM and HLA-DO, which are important in loading the antigenic peptides generated from pathogens onto the HLA molecules of antigen-presenting cell.
HLA types were important in matching tissues and organs for donation and organ transplantation under outdated immunosuppression protocols. Currently, only zero mismatch (six haplotype match) is generally regarded as relevant. Direct crossmatch and blood type matching are still used.
HLA functions
The proteins encoded by HLAs are the proteins on the outer part of body cells that are (effectively) unique to that person. The immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that person's HLA type belongs to that person (i.e., is not an invader). Any cell displaying some other HLA type is "not-self" and is an invader. HLA types are inherited, and some of them are connected with autoimmune disorders and other diseases. Scientists think that people with certain types of HLA antigens are more likely to develop certain autoimmune diseases, such as SLE (Lupus), Myasthenia Gravis, and Sjogren's Syndrome.
When a foreign pathogen enters the body, specific cells called antigen-presenting cells (APCs) engulf the pathogen through a process called phagocytosis. Proteins from the that pathogen are digested into small pieces (peptides) and loaded onto HLA antigens (specifically class II MHC). They are then displayed by the APCs for certain cells of the immune system called T cells, which then produce a variety of effects to eliminate the pathogen.
Through a similar process, proteins (both native and foreign, such as the proteins of viruses) produced inside most cells are displayed on HLA antigens (specifically class I MHC) on the cell surface. Infected cells can be recognized and destroyed by components of the immune system.
External links
- Anthony Nolan Trust: HLA Informatics Group (http://www.anthonynolan.org.uk/HIG/)
- European Bioinformatics Institute IMGT/HLA Sequence Database (http://www.ebi.ac.uk/imgt/hla/)
- American Society for Histocompatibility and Immunogenetics (http://ashi-hla.org)
- European Federation for Immunogenetics (http://www.efiweb.org)