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Human leukocyte antigens (HLA): A roadmap

Sebastien Viatte, MD, PhD
Section Editor
Peter H Schur, MD
Deputy Editor
Paul L Romain, MD


The major histocompatibility complex (MHC) is a term used to describe a group of genes in animals and humans that encode a variety of cell surface markers, antigen-presenting molecules, and other proteins involved in immune function. The human leukocyte antigen (HLA) complex is synonymous with the human MHC.

The earliest HLA associations with rheumatic diseases, such as the association of the HLA-B*27 allele at the HLA-B gene with ankylosing spondylitis (AS) risk and the association of the HLA-DRB1*04 allele at the HLA-DRB1 gene with rheumatoid arthritis (RA), were discovered several decades ago. As the study of HLA genetics has evolved and expanded, the nomenclature has been continually altered, posing challenges for those attempting to follow the science. However, knowledge concerning this genetic region has evolved sufficiently, so the overall nomenclature should be more stable in the future, even though new alleles will be identified and catalogued.

The genetics, nomenclature, and typing of HLA, as well as the relationships between HLA and rheumatic disease, are discussed here. The older nomenclature that may still be encountered in the literature is defined. The specific function of the MHC system, including the mechanisms of antigen presentation, is discussed separately. (See "Major histocompatibility complex (MHC) structure and function".)


The major histocompatibility complex (MHC) in humans refers to a genetic region containing hundreds of genes, including the human leukocyte antigen (HLA) genes (figure 1). Thus, the human MHC region is also referred to as the HLA region. HLA genes express their gene products on the surface of white blood cells (hence the name "human leukocyte antigen," although HLA class I genes (see 'Class I region' below) are also expressed on all nucleated cells) and were originally recognized to contain the genes encoding "tissue antigens" or "tissue types." The function of these genes was revealed in rodent studies, in which they were identified as the factors responsible for rejection of tissue grafts between unmatched individuals (hence the name "major histocompatibility").

The HLA region lies on the short arm of chromosome six at position 6p21.3. The classical MHC spans 3.6 megabases (Mb) and comprises more than 200 genes, including many immune system genes, but also many genes without any known immune function. The localization of genes relevant to the MHC outside the classical boundaries of this region and confirmation of extended linkage disequilibrium have since led to the proposal for an extended MHC (xMHC). This region spans 7.6 Mb and contains over 400 loci. The complete structure and gene map of the HLA region have been published [1,2].

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Literature review current through: Nov 2017. | This topic last updated: Dec 02, 2017.
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