MHC II MHC Class II,HLA-DP,-DQ & -DR (human),I-A & I-E(mouse), RT1B & RT1D(rat)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Dendritic Cell
B Cell
Monocyte
Macrophage
Myeloid Cell
Erythroid Cell
Precursor Cell
Epithelial Cell
T Cell, Activated
Fibroblast
Endothelial Cell
Cytokine
25 / 40

Expression
MHC class II molecules are expressed on dendritic cells, B cells, monocytes, macrophages, myeloid and erythroid precursors and some epithelial cells.  MHC class II is expressed on activated T cells in the human and rat.  Expression of MHC class II is regulated by cytokines including IFNg, which also induces expression of fibroblasts, epithelial and endothelial cells.  MHC class II is expressed on resting T cells in the dog, cat and horse.  In the pig there may be differential expression of MHC class II genes.

Structure
MHC class II is a type 1 glycoprotein.  The molecules are heterodimers of non-covalently associated a and b chains.  Both chains are comprised of 2 IgSF domains and have transmembrane sequences and short cytoplasmic tails.  Multiple alleles of a and b chains exist and they are highly polymorphic.  Because of the extensive polymorphism of MHC class II molecules, accession numbers and sequence data are not included.  Crystal structure of the MHC class II antigen HLA-DR1 is a similar structure to that of the MHC class antigen HLA-A2. The crystals contained dimers of the ab  heterodimer.  Polymorphic residues are positioned at the peptide antigen binding site.  Unlike MHC class I, length is not critical for peptides bound to MHC class II and they make several contacts along the length of the peptide binding groove.  MHC class II molecules are first associated with CD74, the invariant or Ii chain, in the endoplasmic reticulum.  CD74 is degraded in the endosomal/lysosomal pathway leaving a CLIP, MHC class II-associated Ii chain, peptide attached to the MHC class II molecule.  The CLIP peptide is dissociated by binding to class II-related HLA-DM and replaced by peptides generated from exogenous proteins.

MOLECULAR MASS
Cell Type Unreduced Reduced
a chain 33 - 35 kDa
b chain 28 - 30 kDa



Ligands
The peptide antigen bound to MHC class II binds to TCR on CD4+ cells. The affinity of the interaction between the TCR and the MHC/peptide complex is in the range of 10-7 - 10-4 M. Superantigens as intact proteins bind to MHC class II differently from peptides. CD4 interacts directly with non-polymorphic residues on MHC class II and both domain 1 and 2 of the b  chain are implicated in binding.

Function
MHC class II molecules present exogenously derived antigen to CD4+ T lymphocytes, which are usually helper T cells. MHC class II molecules expressed on thymic stromal cells play a key role in the positive and negative selection of CD4+ T cells during thymopoiesis and genetically engineered mice that do not express MHC class II antigens lack CD4+ T cells in the periphery. Signaling can occur through MHC class II.

Comments

 

Certain HLA class II molecules are associated with autoimmune diseases such as coeliac disease, insulin-dependent diabetes mellitus, rheumatoid arthritis, myasthenia gravis, multiple sclerosis and pemphigus vulgaris.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
Antibodies
21-1A6   View Reactivity
28.1   View Reactivity
2C4   View Reactivity
37.68   View Reactivity
38.27   View Reactivity
42.3   View Reactivity
49.1   View Reactivity
BAQ150A   View Reactivity
BB7.1   View Reactivity
CA2.1C12   View Reactivity
CAG5-3D1   View Reactivity
CAT82A   View Reactivity
CI.13.l   View Reactivity
EqT2   View Reactivity
G46-6   View Reactivity
H34A   View Reactivity
H42A   View Reactivity
K274.3G8   View Reactivity
L243   View Reactivity
MSA3   View Reactivity
PG173A   View Reactivity
SPV-L3   View Reactivity
SW73.2   View Reactivity
TH12A   View Reactivity
TH14B   View Reactivity
TH16B   View Reactivity
TH21A   View Reactivity
TH22A5   View Reactivity
TH81A5   View Reactivity
TU169   View Reactivity
Tu36   View Reactivity
TU39   View Reactivity
vpg3   View Reactivity
VPM36   View Reactivity
VPM37   View Reactivity
VPM41   View Reactivity
VPM54   View Reactivity
YKIX334.2   View Reactivity

Revised June 25, 2008


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