MHC I MHC Class I,HLA-A,-B and -C(human), H-2K,-D,-L(mouse), RT1A, RT1C(rat)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Nucleated Cell
Ubiquitous, Erythrocytes Negative
10 / 15
40 / 45

Expression
The "classical" MHC class I molecules, HLA-A, -B and -C in man, are expressed on most nucleated cells but expression varies on different cell types.  IFN- a, b and TNFa increase the expression of MHC class I molecules.  Expression can be low on virus-infected or tumor cells.  "Non-classical" MHC molecules generally have a broad distribution.  HLA-G is expressed only on cytotrophoblasts.

Structure
MHC class I is a type 1 glyocoprotein.  The molecules consist of heterodimers of highly polymorphic a chains non-covalently associated with the invariant b2-microglobulin subunit.  b2-microglobulin and the a3 domain are Ig-related and of the C1-set. The a1 and a2 domains form a platform consisting of a single b pleated sheet topped by a helices.  A groove between the 2 a  helices binds peptides.  The polymorphic aa of class I molecules are concentrated along the peptide binding groove.  Endogenous proteins in the cell are degraded by proteasomes and resultant peptides transport by TAP proteins to be assembled in MHC class I molecules before being expressed stably on the cell surface.  Peptides are usually 9 aa residues long and anchored via residues, typically 2 and 9, in pockets on the peptide binding groove, "non-classical" MHC molecules have a similar structure to "classical" MHC molecules.

MOLECULAR MASS
Cell Type Unreduced Reduced
a chain 44 kDa
b2-microglobulin 12 kDa



Ligands
Peptide antigen bound to MHC class I antigens is recognized by the a/bTCR on CD8+ T cells heterodimers. The affinity of the interaction between the TCR and the MHC/peptide complex is in the range 10-7 - 10-4 M. CD8 interacts with the nonpolymorphic a3 domain.  MHC class I antigens bind the human and mouse NK receptors, CD158 IgSF molecules and Ly-49 C-type lectins respectively.

Function
The "classical" MHC class I molecules present endogenously synthesized peptides to CD8+ lymphocytes, which are usually cytotoxic T cells.  MHC class I molecules expressed on thymic epithelial cells regulate the positive and negative selection of CD8+ T cells during T cell maturation.  Expression of class I molecules depends on the expression of b2-microglobulin and mice lacking a functional b2-microglobulin gene do not express class I molecules on the cell surface.  These animals lack mature CD4-CD8+ T cells and have defective cell-mediated cytotoxicity.  Recognition of MHC class I by NK receptors can protect from lysis by NK cells.

Comments

 

Allogeneic MHC molecules on transplanted organs can induce potent graft rejection.  Certain auto-immune diseases are linked to the MHC class I haplotype, such as ankylosing spondylitis which is linked to HLA-B27.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
Human-HLAA02191P01892M32322
MouseA02182P01887X01838
RatA26842P07151Y00441
Antibodies
2G5   View Reactivity
41.17   View Reactivity
73.2   View Reactivity
B5C   View Reactivity
CF298   View Reactivity
CVS22   View Reactivity
G46-2.6   View Reactivity
H11A   View Reactivity
H17A   View Reactivity
H1A   View Reactivity
H58A   View Reactivity
PT85A   View Reactivity
VPM19   View Reactivity
W6/32   View Reactivity

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University