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Difference between MHC Class I and MHC Class II – MHC Class I vs MHC Class II

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The Major Histocompatibility Complex (MHC) is an extremely connected group of genes throughout all mammal species. The MHC is also known by HLA complex. HLA complex of humans as well as the H-2 complex in mice.

Roles of MHC

  • The development of a cell-mediated and humoral immune response
  • T cells recognize antigens (most T cells can recognize antigen when it is paired in conjunction with MHC molecule)
  • The determination of whether the transplanted tissue can be considered histocompatible, or even histoincompatible

MHC Genes and Their Functions

It’s a collection of genes that are located in a long length of DNA on chromosome 6, that encodes for three types of molecules.

  1. Classes I gene encode glycoproteins which are found on the surface of almost every nucleated cell; the principal function of the class I gene is the delivery of peptide antigens into the cells of the TC.
  2. The Class II MHC genes encode glycoproteins that are expressed mostly on APCs. They deliver processed antigenic peptides to T cells.
  3. The Class III MHC genes encode various secreted proteins with immune functions, which include parts of the immune system as well as proteins that are involved in the process of inflammation (e.g. TNF, Heat Shock proteins).

Difference between MHC Class I and MHC Class II – MHC Class I vs MHC Class II

The major difference in MHC Class I and MHC Class II (including their antigen processing pathways and presentation pathways) can be described by this chart:

CharacteristicsMHC-I molecularMHC II molecular
DistributionThe majority of nucleated cells, including platelets.They have a limited tissue distribution and are mostly found on macrophagesand B cells, dendritic cells and other antigen-presenting cells exclusively.
Encoding genesMHC Class I protein are encoded in the HLA-A as well as HLA B and HLA C genes.MHC Class II proteins are encoded by genes from the HLA-D region.
The antigen’s nature is describedAntigens released through MHC Class I molecules have an an endogenous origin.Antigens that are formulated through MHC Class II molecules originate of extracellular proteins.
AntigenCytosolic proteins. They sample the peptides that are produced within cells or that get into cytosol through phagosomes.Class II molecules are able to detect external peptides like lysosomal proteins, which are most often internalized from the extracellular.
Enzymes that are involved in the production of peptidesCytosolic proteasomeProteases for endosomal and lysosomal
MHC’s peptidide load is a result of peptides.Endoplasmic reticulumSpecialized Vesicular compartment
Peptide-loading complexIt includes the ER transporter that is associated with the antigen process (TAP1/2) as well as tapasin the oxidoreductase ERp57 and the chaperone protein calreticulin.Chaperones in ER Invariant chain in ER Golgi, ER as well MHC Class II compartment/Class I vesicle
Recognizing co-receptorThey are detected by CD8 co-receptors by their MHC Class I b2 subunit.They are detected by CD4 co-receptors via b1 and the b2 subunits.
Receptor T cellAntigens present to T cells with CD8+.Antigens present to T cells with CD4+.
StructureMHC Class I molecules are composed of a single membrane-spanning chain that is produced by MHC genes as well as a b-chain generated by the gene b2-microglobulin.MHC Class II proteins are composed of two chains that span the membrane, both of which are produced through MHC genes.
Building amino acidsHave 8-10 amino acids.Have thirteen to 18 amino acids.
Peptide binding domainsA1 and a2 are binding domains of peptides.A1 and B1 are binding domains of peptides.
Chain that is invariantThere is no invariant chain.It has an invariant chain that is invariant.
Effects of functionalThe presence of a large amount of antigens targets cells for destruction.The presence of foreign antigens triggers production of antibodies.
Detection MethodSerologySerology and mixed lymphocyte response


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