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The 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 the 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; these 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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