Human leukocyte antigens(HLA)
Human leukocyte antigens(HLA)Just as blood group antigens are found on the RBCs, human leukocyte antigens (HLA) are found on the surface of a variety of body cells including leucocytes. The HLA system is divided into two major classes: HLA Class I and HLA Class II antigens The genes that are responsible for the formation of HLA are situated on the short arm of chromosome 6.
The HLA Class I antigens are further divided into HLA-A, HLA-B, and HLA-C sub-classes. Each of these subclasses contains a number of antigens which are numbered as 1,2,3, etc (e.g., HLA A1, HLA B35, HLA C3) HLA Class I antigens are found on the surface of all the nucleated cells and platelets, as opposed to the HLA Class II antigens which have a comparatively restricted distribution. The main function of the HLA Class I antigens is to present antigens to the suppressor/cytotoxic subset of T-lymphocytes. T-lymphocytes cannot see/recognize the antigen unless it is presented to them in combination with HLA antigens. CD8+ suppressor/cytotoxic T-lymphocytes can recognise the antigens when they are presented in combination with HLA Class I antigens. HLA Class I antigens have a major role in initiating the cellular immune response in the case of viral infections or when the cells are changed because of malignant transformation. HLA Class II antigens are sub-divided into HLA-DR, HLA-DP and HLA-DQ groups.
Individual antigens within these groups are numbered (HLA DR1, HLA DP2, HLA DQ3, etc). These molecules present antigens to CD4+ helper/inducer T-lymphocytes. These antigens are prepared after phagocytosis by the macrophages. The helper T-lymphocytes are called ―helper because they start to produce the cytokines (Interferon γ, IL-2, IL-4, IL-10, IL-12, etc) after recognizing the antigens in combination with the HLA Class II molecules. These cytokines help macrophages and cytotoxic/suppressor T-lymphocytes to become more active in their functions. These cytokines are also the main driving force for the sensitized B-lymphocytes to produce antibodies required for the secondary immune response.
The dependence of cellular and humoral (antibody)related functions on the cytokines produced by helper T-lymphocytes makes these cells pivotal in the immune response. Their importance is highlighted in HIV Infection which destroys the helper T-lymphocytes. In patients with advanced HIV Infection, the helper T-lymphocytes number is decreased and, their function is impaired. This results in infections by opportunistic organisms and an increased incidence of malignant disorders.
Importance of HLA in Organ Transplants One of the main functions of the immune system is to differentiate self-tissue from all other kinds of tissues (e.g. transplants). The immune system can recognize the body‘s own tissues by the presence of HLA antigens on their surface. T-lymphocytes recognize the HLA antigens, whenever they come in contact, with the help of their TCRs. All cells displaying the body‘s own HLA antigens are recognised as self and T lymphocytes pass on without getting activated. Thus, the immune response against the body‘s own cells is not initiated. In organ transplants, tissue type (the combination of the HLA antigens--each individual usually carries six HLA Class I and six HLA Class II antigens) is determined by tissue-typing. The tissue type of the recipient and the donor is matched so that when the donor organ is placed inside the recipient‘s body, the recipient‘s immune system recognizes the transplanted organ as self and the immune response is not activated.
Importance of Human leucocyte antigens in Disease
The immune system is largely activated after the presentation of the antigens, along with the HLA, to the T-lymphocytes. That also indicates that if certain types of HLA antigens present more of one type of antigen, then some diseases would be produced either less or more in individuals having a particular kind of the HLA antigen. The most significant HLA association is of HLA B27 with the development of the ankylosing spondylitis (80 times higher risk of developing the disease in HLA B27-positive individuals)
Importance of HLA Genetic Identification of the individuals
The large variety of HLA antigens in each subgroup and the biodiversity of the human population ensure a unique combination of the HLA antigens in one individual. This unique combination may be utilized for medico-legal purposes, though the importance in this respect has diminished with the discovery of other DNA markers.
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