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Human Leukocyte Antigen (HLA) System

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The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is 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 which present antigen (Ag) are divided into 2 major 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 β 2-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, -B, or -C loci. Lymphocytes reactive to class I molecules express CD8 molecules often associated with effector cytotoxic function.

Class II MHC molecules are present on 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.

A group of important inflammatory molecules, called class III MHC molecules, include complement components (eg, C2, C4, factor B), tumor necrosis factor (TNF)-α, and heat shock proteins.

Individual alleles of each locus of 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 Ags (eg, psoriasis to HLA-Cw6, ankylosing spondylitis and reactive arthritis to HLA-B27, narcolepsy to HLA-DR2 and HLA–DQB1*0602, type I diabetes mellitus to HLA-DQ2 and HLA-DQ8, multiple sclerosis to HLA-DR2, RA to HLA-DRB1).

Last full review/revision November 2005

Content last modified November 2005

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