Human Leucocyte Antigen (HLA) System and Human Disorders


The major histocompatibility complex (MHC) has been studied in depth because it is associated genetically with more human disorders than any other region in the human genome. In addition to the human leucocyte antigen (HLA) genes, the MHC contains a diverse array of multiallelic genes, many of which are involved in modulating the immune response to pathogens. Advanced mapping and sequencing approaches are helping to define more precisely contributions of MHC variants to disease. Class I or class II molecules are confirmed as the primary influence in most studies, attesting to their functional impact on antigenic peptide presentation to lymphocytes. Regulatory polymorphism controlling cell surface expression of HLA molecules has also been associated with disease. However, the precise causal nature of the majority of associated alleles and haplotypes with disease is still not understood.

Key Concepts

  • The MHC encodes genes essential for immunity in humans, including the HLA molecules.
  • With the exception of one gene, HLA‐DRA, the classical HLA genes are highly variable.
  • HLA class I and II genes are associated with many diseases, including infectious diseases, cancers and neuropathies but particularly autoimmunity.
  • Many HLA variants are concurrently associated with both infectious and autoimmune diseases.
  • The MHC may be considered as a cluster of genes with integrated functions.
  • A high proportion of MHC genes are involved in immunity.
  • The MHC contains nonclassical class I and II genes, such as HLA‐E, F and G, and HLA‐DM, DO, respectively.

Keywords: human leucocyte antigen; major histocompatibility complex; polymorphism; autoimmunity; antigen presentation

Figure 1. Gene map of the human MHC (major histocompatibility complex) showing the context and organisation of the polymorphic human leucocyte antigen (HLA) gene loci.


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Web Links

HFE (hemochromatosis); MIM number: 235200 OMIM:

HLA‐E (major histocompatibility complex, class I, E); MIM number: 143010. OMIM:

MIC‐A (MHC class I polypeptide‐related sequence A); MIM number: 600169. OMIM:

dbMHC database;

Human leukocyte antigens at the US National Library of Medicine Medical Subject Headings (MeSH);

IPD‐IMGT/HLA Database;

Nomenclature for Factors of the HLA System;

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Traherne, James A(Feb 2018) Human Leucocyte Antigen (HLA) System and Human Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005171.pub2]