MHC Class I vs. MHC Class II Protein

Last updated on June 11th, 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.


  • 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 APCsMHC 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 MHCEndoplasmic reticulumSpecialized vesicular compartment
Molecules involved in transport of peptides and loading of MHC moleculesChaperones, TAP in ERChaperones in ER; invariant chain in ER, Golgi and MHC Class II compartment/Class II vesicle; DM
End ResultPresentation of  foreign-intracellular antigens or altered self-antigens;  targets cell for destructionPresentation of foreign extracellular antigens; induces antibody production, and attracts immune cells to area of infection

References and further reading: 

About Acharya Tankeshwar 473 Articles
Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. I am working as an Asst. Professor and Microbiologist at Department of Microbiology and Immunology, Patan Academy of Health Sciences, Nepal. If you want me to write about any posts that you found confusing/difficult, please mention in the comments below.


  1. Hlo sir…
    Could you suggest me about antibiotic sensitivity test for bacteria…. I can’t found anything about this test
    I wana find out the bacteria that produce antibiotics…so plz sir help me..

    • Hi, you can find antibiotic producing bacteria by the following procedure.
      1. select source mean sample area.
      2. make lawn of bacteria and spread very little amount of sample over lawan.
      3. incubate for 24hrs and then check result.
      4. there will lot of growth on the medium if you find zone of inhibition on plate, take that colony for sure that one is antibiotic producers.

  2. Source of protein antigens: I thought that MHC1 presented peptides from internal proteins, the majority from failed manufactured proteins in the ER. MHC11 are for presenting peptides that have been internalised such as viruses . Haven’t you got them the wrong way round?

    • Dear Henry Mannings
      Thank you so much for your comment and making me aware about the mistakes done while posting this blog. With your help, now i became able to correct the exchanged information. I will be looking for your feedback and suggestions in future too.

  3. Please help me to answer these questions.
    Why is always mycobacterium tuberculosis( acid fast bacilli) is not matching with gram staining ? And what category is standing for as bacteria gram activities ?

    • Hello sir ,

      Why mycobacteria tuberclusosis does not staining with gram staining ?

      Which gram staining is mycobacteria tuberclusosis ?

  4. Hello sir, can you help me suggest a reason for why different MHC class 1 molecules between donor and recipient cells can lead to rejection of a transplanted organ or tissue ?

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