Major Histocompatability Complexes

()Map\Tab IMMUNOLOGY (Map/Tab) ADAPTIVE IMMUNE SYSTEM

Structure and Function of MHC Class I

Structure

• MHC class I is expressed on virtually all nucleated cells.
• MHC class I consists of a membrane-associated heavy chain bound non-covalently with a secreted light chain.
  • Heavy chain:
    • Made up of three distinct extracellular protein domains.
      • α1, α2 and α3.
    • The C- terminus is cytoplasmic.
  • Light chain:
    • Known as β2-microglobulin.
    • Similar in structure to one of the heavy chain domains.
    • Not membrane associated.
      • But binds to the α3-domain of the heavy chain.
• The MHC class I domains are structurally and genetically related to immunoglobulin and TcR domains.
  • The outer domains (α1 and α2) are like the variable domains.
  • The α3 domain and β2m are like thrconstant domains.
• MHC class I molecules are folded to form specific 3-dimensional structures.
  • The α1 and α2 domains are folded to produce an antigen-binding groove.
    • This groove can bind molecules of a limited size only.
      • 8-10 amino acids.
      • This limits the size of epitope seen by the T-cell receptors.

Function

• MHC class I molecules bind antigenic peptides derived from within the cell and present these to the T-cell receptors of CD8+ T-cells.
  • E.g. virus-encoded antigen.
• Endogenously produced proteins are produced in the cell cytoplasm.
  • Intracellular pathogens utilise this cellular metabolic machinery for protein synthesis.
  • Many of the proteins synthesised are not used and are re-utilised by the cell.
    • Peptides from these proteins are transported to the Golgi apparatus by specific transporter molecules.
    • These peptides then interact with newly synthesized MHC class I molecules.
• Only MHC class I that is associated with peptide will be expressed at the surface.
  • The immune system is therefore able to see antigen from intracleeular pathogens.