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The human leukocyte antigen system (sometimes human lymphocyte antigen) (HLA) is the general name of a group of genes in the human Major Histocompatibility Complex (MHC) region on human chromosome 6 (mouse chromosome 17) that encodes the cell-surface antigen-presenting proteins. These proteins are sometimes designated the Mhc, although this convention is rarely observed.

Layman's explanation

Human Leukocyte Antigen, or HLA, is a class of protein which is often found on the surface membrane of cells, and which serves the purpose of "presenting" possible antigen to T and B cells. There are different sorts of HLA - class I HLA and class II HLA - and they each work slightly differently.

Both do essentially the same job though. They sit inside a cell, and have a groove in which they can attach little bits of protein. (These bits of protein will have come from outside the cell or could be products of the cell's own genes.) Once a bit of protein (or other possible antigen) is attached, the HLA moves out and sits on the outside of the cell, so that a T cell can come along and check the molecule that is being presented. The T cells, in their turn, check whether the molecule is "self" or foreign, and will either pass over it or react to its presence (either destroying the cell, or raising the alarm about the foreign substance by emitting cytokines).

Classification of HLAs/alleles

"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HLA types were important in matching tissues and organs for donation and organ transplantation under outdated immunosuppression protocols.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 (and therefore 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 erythematosus), Myasthenia Gravis, and Sjrogren'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 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.

HLA antibodies

HLA antibodies are typically not naturally occurring, with few exceptions are formed as a result of an immunologic challenge of a foreign material containing non-self HLAs via blood transfusion, pregnancy (paternally-inherited antigens), or organ or tissue transplant.

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