Difference between MHC Class I and MHC Class II Proteins

Last updated on May 10th, 2021

Major Histocompatibility Complex (MHC) is a tightly linked cluster of genes present in every mammalian  species. The MHC is referred to as the HLA complex in humans and the H-2 complex in mice.

Roles:

• Development of humoral and cell-mediated immune response
• Antigen recognition by T cells (most T cells recognize antigen only when it is combined with MHC molecule)
• Determining whether transplanted tissue will be histocompatible or histoincompatible

MHC Genes and Functions:

It is a collection of genes within a long stretch of DNA on chromosome 6, which codes for 3 classes of molecules

1. Class I MHC genes: encode glycoproteins expressed on the surface of nearly all nucleated cells; the major function of the class I gene product is presentation of peptide antigens to TC cells.
2. Class II MHC genes encode glycoproteins expressed primarily on APCs, where they present processed antigenic peptides to TH cells.
3. Class III MHC genes encode, various secreted proteins that have immune functions, including components of the complement system and molecules involved in inflammation (e.g. TNF, Heat Shock proteins).

Major difference between MHC Class  I and MHC Class II (including their antigen processing and presentation pathway) is summarized in this table:

	MHC Class I	MHC Class II
Structure	MHC class I molecules consist of one membrane-spanning α chain (heavy chain) produced by MHC genes, and one β chain (light chain or β2-microglobulin) produced by the β2-microglobulin gene.	MHC class II molecules consist of two membrane-spanning chains, α and β, of similar size and both produced by MHC genes.
Types of APCs	MHC I glycoproteins are present in all nucleated cells.	MHC II glycoproteins are only present on specialised antigen-presenting cells (APCs), including macrophages that engulf foreign particles such as bacteria, dendritic cells that present antigen to T cells, and B cells that produce antibodies.
Nature of Antigen Presentation	MHC class I glycoproteins present endogenous antigens that originate from the cytoplasm.	MHC II proteins present exogenous antigens that originate extracellularly from foreign bodies such as bacteria.
Size of peptide	MHC Class I present 8-10 amino acid peptides	MHC Class II presents 14-18 amino acid peptides.
Responsive T Cells	Present antigen to cytotoxic T cell lymphocytes (CD8+ T Cells);	Present antigen to helper T cell lymphocytes; (CD4+ T cells).
Co-receptor responsible	Binds with CD8 coreceptors molecules on cytotoxic T cells	Binds with CD4 co-receptors molecules on helper T cells
Sources of Protein Antigens	Cytosolic proteins (mostly synthesized in the cell, may enter cytosol from phagosomes)	Endosomal/lysosomal proteins (mostly internalized from extracellular environment)
Enzymes Responsible for peptide generation	Cytosolic proteasome	Endosomal and lysosomal proteases (e.g., cathepsins)
Site of peptide loading of MHC	Endoplasmic reticulum	Specialized vesicular compartment
Molecules involved in transport of peptides and loading of MHC molecules	Chaperones, TAP in ER	Chaperones in ER; invariant chain in ER, Golgi and MHC Class II compartment/Class II vesicle; DM
End Result	Presentation of  foreign-intracellular antigens or altered self-antigens;  targets cell for destruction	Presentation of foreign extracellular antigens; induces antibody production, and attracts immune cells to area of infection

References and further reading: 

• Cellular and Molecular Immunology, 9th Edition
• Kuby Immunology, 8th Edition
• Roitt’s Essential Immunology, 13th Edition