MHC Class I vs MHC Class II- Definition, 15 Major Differences, Examples

Last Updated on December 30, 2020 by Sagar Aryal

MHC Class I and Class II differences (mhc i vs mhc ii)

Differences between MHC Class I and Class II

The major differences are:


Characteristics MHC-I molecule

MHC -II molecule

1. Distribution Present on almost all nucleated cells including platelets. Have a restricted tissue distribution and are chiefly found on macrophages, dendritic cells, B cells, and other antigen-presenting cells only.
2. Encoding genes MHC class I proteins are encoded by the HLA-A, HLA-B, and HLA-C genes. MHC Class II proteins are encoded by the genes of the HLA-D region.
3. Nature of antigen presented Antigens presented by MHC class I molecules are of endogenous origin. Antigens presented by MHC class II molecules are derived from extracellular proteins.
4. Antigen Cytosolic proteins; they sample peptides generated within the cell or those that may enter cytosol from phagosomes. Class II molecules sample peptides outside the cell such as lysosomal proteins mostly internalized from extracellular environment.
5. Enzymes involved in peptide generation  Cytosolic proteasome  Endosomal and lysosomal proteases
6. Peptide loading of MHC Endoplasmic reticulum Specialized vesicular compartment
7. Peptide-loading complex Includes the ER transporter associated with antigen processing (TAP1/2), tapasin, the oxidoreductase ERp57, and the chaperone protein calreticulin. Chaperones in ER; invariant chain in ER, Golgi and MHC Class II compartment/Class II vesicle
8. Recognizing co-receptor They are recognized by CD8 co-receptors through the MHC Class I β2 subunit. They are recognized by CD4 co-receptors through β1 and β2 subunits.
9. Receptor T cell Present antigens to CD8+ T cells. Present antigens to CD4+ T cells.
10. Structure MHC class I molecules consist of one membrane-spanning α chain produced by MHC genes, and one β chain produced by the β2-microglobulin gene. MHC class II molecules consist of two membrane-spanning chains, α and β both produced by MHC genes.
11. Building amino acids Possess 8-10 amino acids. Possess 13-18 amino acids.
12. Peptide binding domains  α1 and α2 are peptide binding domains. α1 and β1 are peptide binding domains.
13. Invariant chain Has no invariant chain. Has an invariant chain.
14. Functional effect Presence of abundant antigens target cell for destruction. Presences of foreign antigens induce antibody production.
15. Detection Method Serology Serology and mixed lymphocyte reaction


  1. Brooks, G. F., Jawetz, E., Melnick, J. L., & Adelberg, E. A. (2010). Jawetz, Melnick, & Adelberg’s Medical Microbiology. New York: McGraw Hill Medical.
  2. Chelbi, S., Dang, A., & Guarda, G. (2017). Emerging Major Histocompatibility Complex Class I -Realted Functions of NLRC5. Advances in Immunology , 133, 89-119.

MHC Class I and Class II differences (mhc i vs mhc ii)

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