[Human major histocompatibility complex: the HLA system]

The HLA (human leukocyte antigens) system, or human major histocompatibility complex, is the most polymorphic functional genetic entity known at present. It consists of HLA class I genes and molecules (A, B and C) which control CD8+ cell-mediated antiviral responses, and class II genes and molecules (DR, DQ and DP) which control CD4+ cell responses (anti-bacterial and anti-toxin). HLA molecules function by presenting antigenic peptides to CD8+ cells (class I) and CD4+ cells (class II). Antigen presentation depends on the intracellular location of the antigen. Antigens present in the exocytosis pathway are presented by class I molecules, while class II molecules present antigens associated with the endocytosis pathway. More than 200 alleles have been detected by means of serological testing (microlymphocytotoxicity) and biochemical methods (IEF) in the HLA class I system, and now by means of molecular biology techniques for class II molecules (PCR-SSO and PCR-RFLP). This molecular typing has revealed the amino acids in HLA molecules that confer genetic susceptibility or resistance to numerous HLA-associated diseases. This is the case for example of ankylosing spondylitis (region 45-46 of HLA-B27 molecules), juvenile diabetes (aa 57 of D beta Q) and rheumatoid arthritis (aa 65-71 of DR beta). Thus, the HLA system is a genetic tool for diagnostic and therapeutic decision-making.