The human leukocyte antigen system (HLA) is the name of the human major histocompatibility complex (MHC). This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and many other genes. Aside from the genes encoding the 6 major antigens, there is a large number of other genes, many involved in immune function located on the HLA complex. Diversity of HLA in human population is one aspect of disease defense, and, as a result, the chance of two unrelated individuals having identical HLA molecules on all loci is very low, except for non-identical siblings, which have a 25% chance of being HLA-identical.
Importance of HLA allelic variation
Studies of humans and other animals infer a heterozygous selection mechanism operating on these loci as an explanation for this exceptional variability. One credible mechanism is sexual selection in which females are able to detect males with different HLA relative to their own type. While the DQ and DP encoding loci have fewer alleles combinations of A1:B1 can produce a theoretical potential of 1586 DQ and 2552 DP αβ heterodimers, respectively. While certainly nowhere near this number of isoforms exist in the human population, each individual can carry 4 variable DQ and DP isoforms increasing the potential number of antigens that these receptors can present to the immune system in individual immune system. Studies of the variable positions of DP, DR, and DQ reveal that peptide antigen contact residues on Class II molecules are most frequently the site of variation in the protein primary structure. Therefore, through a combination of intense allelic variation and/or subunit pairing the Class II 'peptide' receptors are capable of binding an almost endless variation of peptides of 9 amino acids or longer in length, protecting interbreeding subpopulations from nascent or epidemic diseases. Individuals in a population have frequently different haplotypes and as a result many combinations, even in small groups, affords the survival of the groups and thwarts evolution of epitopes in pathogens to hide from the immune system.
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).
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.
HLA Informatics Group at The Anthony Nolan Trust IMGT/HLA Sequence Database at European Bioinformatics Institute American Society for Histocompatibility and Immunogenetics European Federation for Immunogenetics HistoCheck HLA matching tool for organ and stem cell transplantation Allele Frequencies at Variable Immune related Loci MeSH Human+leukocyte+antigens
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Antibodies to HLA 1
Antibodies to HLA 2