Major Histocompatibility Complex MHC Molecules

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Major Histocompatibility Complex (MHC) Molecules

• February 6, 2001

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MHC Molecules

• Tightly linked, polymorphic gene cluster encodes
  glycoprotein members of the Ig superfamily
• Found on chromosome 6 in humans and chromosome 17
  in mice
• Serve as structural anchors for processed
  antigen the surface of cells
• Essential for both humoral and cellular immunity
• Play crucial role in normal immune response,
  autoimmunity (differentiation between foreign and
  self) and tissue rejection, among others

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MHC Class I and Class II Molecules

• MHC Class I
• Expressed on nearly all nucleated cells
• Major function is to present processed antigen to
  CD8 T cells (Tc Cells)
• Consist of a chain and b2-microglobulin

• MHC Class II
• Expressed primarily on APCs (mf, dendritic cells
  and B cells)
• Major function is to present processed anti-gen
  to CD4 T cells (Th cells)
• Consist of a chain and b chain

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Haplotypes

• Many alleles exist at each gene locus. These
  alleles are inherited as sets from each parent.
  Each set is referred to as a haplotype.
• In inbred mice, both haplotypes are identical

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Both Class I and Class II MHC bind peptides
strongly in physiological conditions
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Kinetics of MHC Class II Expression

• Professional APCs (e.g. dendritic cells)
  express MHC Class II constitutively
• MHC Class II is expressed on mature B cells, but
  not on pre-B cells
• Monocytes and macrophages which have not
  interacted with antigen express low levels of MHC
  Class II, but the levels increase dramatically
  after activation

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Something to think about
Upon infection by certain viruses (e.g.
cytomegalovirus (CMV) and hepatitis B) MHC
expression is dramatically reduced. WHY?
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MHC Class III Molecules

• Include several complement proteins, TNF-a and
  TNF-b (inflammatory cytokines) and two heat shock
  proteins (HSPs)
• MHC Class III proteins are not membrane proteins
  and are not related in structure to MHC Class I
  and MHC Class II proteins
• Do not present antigen, although many are
  involved in some way with the immune response