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The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is controlled by genes located on chromosome 6. It encodes cell surface molecules specialized to present antigenic peptides to the T-cell receptor (TCR) on T cells. MHC molecules that present antigen (Ag) are divided into 2 main classes.
Class I MHC molecules are present on the surface of all nucleated cells and platelets. These polypeptides consist of a heavy chain bound to a β2-microglobulin molecule. The heavy chain consists of 2 peptide-binding domains, an Ig-like domain, and a transmembrane region with a cytoplasmic tail. The heavy chain of the class I molecule is encoded by genes at HLA-A, HLA-B, and HLA-C loci. Lymphocytes that express CD8 molecules react with class I MHC molecules. These lymphocytes often have a cytotoxic function, requiring them to be capable of recognizing any infected cell. All nucleated cells express class I MHC molecules and can thus act as antigen-presenting cells for CD8 T cells (CD8 binds to the nonpolymorphic part of the class I heavy chain). Some class I MHC genes encode nonclassical MHC molecules, such as HLA-G (which may play a role in protecting the fetus from the maternal immune response) and HLA-E (which presents peptides to certain receptors on natural killer cells).
Class II MHC molecules are usually present only on professional Ag-presenting cells (B cells, macrophages, dendritic cells, Langerhans' cells), thymic epithelium, and activated (but not resting) T cells; most nucleated cells can be induced to express class II MHC molecules by interferon (IFN)-γ. Class II MHC molecules consist of 2 polypeptide (α and β) chains; each chain has a peptide-binding domain, an Ig-like domain, and a transmembrane region with a cytoplasmic tail. Both polypeptide chains are encoded by genes in the HLA-DP, -DQ, or -DR region of chromosome 6. Lymphocytes reactive to class II molecules express CD4 and are often helper T cells.
The MHC class III region of the genome encodes several molecules important in inflammation; they include complement components C2, C4, and factor B; tumor necrosis factor (TNF)-α; lymphotoxin-α; lymphotoxin-β; and 3 heat shock proteins.
Individual alleles of the class I and II loci in the HLA system are given standard designations (eg, HLA-A1, -B5, -Cw1, -DR1). Alleles defined by DNA sequencing are named to identify the gene and to give each allele a unique number composed of the HLA locus, an asterisk, 2 numbers representing the serologic equivalent of the Ag, and 2 numbers representing the specific allele (eg, A*0201, DRB1*0103, DQA1*0102). Sometimes another number is added to identify a different subtype.
Some disorders are linked to specific HLA alleles (eg, psoriasis to HLA-Cw6, ankylosing spondylitis and reactive arthritis to HLA-B27, narcolepsy to HLA-DR2 and HLA–DQB1*0602, type 1 diabetes mellitus to HLA-DQ2 and HLA-DQ8, multiple sclerosis to HLA-DR2, RA to HLA-DRB1).
Last full review/revision September 2008 by Peter J. Delves, PhD
Content last modified September 2008
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