Saturday, 16 January 2021

Structure and Difference Between MHC Class 1 and MHC Class 2 molecules

  MHC (major histocompatibility complex) is a tightly linked complex of genes. These genes will be encoding for proteins that are expressed on the cell surface and this perticular cell surface proteins are really important for Antigen presentation and rapid graph rejection. These MHC genes are present on Chromosome 6.

MHC genes encodes MHC molecules which are expressed on cell surface. In case of a foreign antigen, which is comming inside the cell will broke it down into smaller peptides. These peptides then bind to the MHC molecules and these MHC molecules present a small peptide or a small fragment of this antigen on the cell membrane for recognition by respective
T-cell.


Structure of MHC Class-I Molecule :

  MHC (Major Histocompatibility Complex) molecules are present on the cell membrane.
MHC Class I molecule contains one alpha(α) chain and one beta(β) chain
Alpha chain is of 45 kDa. This alpha chain is divided in 3 segments -
  1) Extracellular segment,
  2) Transmembrane segment,
  3) Cytoplasmic tail segment.

The Extracellular segment consist of 3 domain that is α1, α2, and α3 domains. Each of these domain contains approximately of 90 amino acids. The alpha chain is inserted into the cell membrane through a Transmembrane domain of 25 amino acid. The entire structure has a cytoplasmic tail of 30 amino acids.

The α3 domain is invariant and it contains binding site for the cytotoxic T-cell (CD8+). The peptide binding cleft is present between alpha-1 and alpha-2 domain and it is closed both ends.

Along with the α chain MHC Class-1 molecules show the presence of a small β2 microglobin chain of 12 kDa. This
β2 microglobin has a non covalent interaction with the α3 is very essential for the expression of MHC Class 1 molecule on the cell surface. If β2 and α3 are not interacting then no active MHC molecule can be formed. After a peptide is bound to the peptide binding cleft, the MHC Class 1 structure is transported to the cell membrane and the antigen is presented to the respective T-cell.


Structure of MHC Class-II Molecule :


  MHC Class-II molecule consist of an alpha (α) chain and a beta (β) chain both of which are embedded into the cell membrane. Both the alpha chain and beta chain consist of three segment which are -
  1) Extracellular segment,
  2) Transmembrane segment,
  3) Cytoplasmic tail segment.

Alpha chain is of 33 kDa, and it has two external domains
α1 and α2. Where β chain is of 28 kDa. and it has two external domains β1 and β2.

In MHC Class 2 molecule β2 domain contains the binding site for T-helper cell. In MHC Class 2 molecule peptide binding cleft is presented between α1 and β2 domain and this is open at both ends. This peptide binding cleft can accomodate peptide of the size 13 to 18 amino acids in length.


Difference Between MHC Class 1 and MHC Class 2 Molecules :

- MHC Class 1 molecule is Expressed on Nucleated cells. while, MHC Class 2 molecule Expressed on Antigen presenting cells(APCs)

- External domain of MHC Class 1 molecules contains membrane bound glycoprotein (α chain of 45 kDa) associated non-covalently with β2 microglobulin (12 kDa).
While, external domain of MHC class 2 molecule contains 2 different glycoproteins α chain (33kDa) and β chain (28kDa).

- MHC Class 1 molecule α chain has 3 external domain.
MHC Class 2 molecule α and β chain have 2 external domain each.

- MHC Class 1 molecules are Encoded by B, C and A genes located at telomeric end on chromosome 6 in human.
MHC Class 2 molecule are Encoded by DP, DQ and DR genes located at centromeric end on chromosome 6 in human.

- In MHC Class 1 molecule Peptide binding is located between α1 and α2 domain.
while, In MHC Class 2 molecule peptide binding is located between α1 and β1 domain.

- Peptide binding cleft closed at both the end in MHC Class 1 molecule and it is open in MHC Class 2 molecules.

- Nature of bound peptide in MHC Class 1 molecule is Extended structure in which both ends interact with MHC cleft but middle arches up away from MHC molecules. While in MHC Class 2 molecule Extended structure is held to a constant elevation above the floor of MHC cleft.

- MHC Class 1 molecule generate Cell mediated immune response, while MHC Class 2 molecules generate Humoral immune response.

- The source of Peptide in MHC Class 1 molecule is Endogenous origin. While in MHC Class 2 molecule it is Exogenous origin (self or non self).

- MHC Class 1 molecules are present antigen to Cytotoxic Tc (CD8+) cells.
MHC Class 2 molecules are present antigen to Helper Th(CD4+) cells.

- Binding site of respective T cells in MHC Class 1 molecule is at α3 domain. while in MHC Class 2 binding site of respective T cell in β1 domain.


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