Major Histocompatibility Complex

Aka: Major Histocompatibility Complex, Major Histocompatibility Complex Antigen, Human Leukocyte Antigen, HLA Complex, MHC-Antigen complex, Histocompatibility Antigen Class I Molecule, HLA Class 1, MHC Class I, MHC-1, MHC Class 1, MHC Class 1 - Antigen Complex, Major Histocompatibility Complex Class 1 Protein, Histocompatibility Antigen Class II Molecule, HLA Class 2, MHC Class 2, MHC Class II, MHC-2, MHC Class 2 - Antigen Complex, Major Histocompatibility Complex Class II Protein

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II. Definitions

  1. Major Histocompatibility Complex or MHC (Human Leukocyte Antigen or HLA Complex)
    1. Polymorphic genes located on Chromosome 6 short arm
    2. MHC genes encode Glycoproteins MHC Class 1 and MHC Class 2
  2. Human Leukocyte Antigen (HLA)
    1. Antigens processed (converted to peptides) and presented via MHC molecules on surface of Antigen Presenting Cells (APC)

III. Physiology: MHC Haplotypes

  1. Each person has 2 sets of MHC genes (one on each Chromosome 6)
  2. Each Chromosome 6 encodes three MHC-1 genes and three MHC-2 genes
    1. For each of the 6 encoded genes many variations exist
    2. The 6 encoded MHC gene variants (or Alleles) on each Chromosome are inherited as a group (haplotype)
  3. Each MHC haplotype represents a unique collection of Alleles
    1. One MHC haplotype is inherited from one the father's 2 Chromosome 6, and one haplotype from the mother

IV. Types: MHC Class 1

  1. Function
    1. Presents peptides from processed endogenous Antigen (e.g. Intracellular Bacteria, intracellular Parasites, viruses)
    2. May be expressed on surface of any nucleated host cell
    3. Part of Cytosolic Pathway in which peptides are presented to CD8+ T-Cells (Cytotoxic T-Cells)
  2. Comprised of 2 polypeptide chains
    1. B2-Microglobulin Chain (12 kd)
    2. Alpha (heavy chain, 45 kd)
      1. Three subunits (a1, a2, a3)
      2. a3 is bound to cell membrane
      3. a1 and a2 together form a cleft between them that serves as the peptide binding site
  3. Genes (each group is inherited as part of a unique haplotype)
    1. HLA-A
    2. HLA-B
    3. HLA-C

V. Types: MHC Class 2

  1. Function
    1. Presents peptides from processed exogenous Antigen (extracellular Antigens)
    2. MHC-1 is expressed only on surface of Dendritic Cells, Macrophages, B-Cell (B-Lymphocyte)
    3. Part of Endocytic Pathway in which peptides are presented to CD4+ T-Cells (T-Helper Cells)
  2. Comprised of 2 polypeptide chains (alpha and beta)
    1. Alpha and Beta each have 2 subunits (a1, a2 and b1, b2)
    2. Subunits a2 and b2 are bound to cell membrane
    3. Subunits a1 and b1 together form a cleft between them that serves as the peptide binding site
  3. Genes (each group is inherited as part of a unique haplotype)
    1. HLA-DP
    2. HLA-DQ
    3. HLA-DR

VI. References

  1. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL
  2. Guyton and Hall (2006) Medical Physiology, p. 419-50

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