Difference between MHC Class I and MHC Class II Proteins

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.


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

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