Question

3. Describe the structure of a class I MHC molecule AND a class II MHC molecule with the following prompts:

a. number of polypeptide chains

b. domains of each polypeptide chain, including transmembrane and cytosolic domains

c. secondary structure

d. domain composition of the peptide-binding site

e. details of the architecture of the peptide-binding site

f. size of the peptide that can bind

Answer 1

Major histocompatibility complex (MHC) are responsible for antigen presentation by professional antigen presenting cells such as macrophages and dendritic cells and other nucleated cells.

MHC's are polymorphic (multiple alleles of present in the host chromosome which and coats MHC) and codominant(both paternal and maternal alleles are equally expressed).

MHC class I:

• It includes three different alleles that is HLA A,B and C.
• Express on all nucleated cells.
• MHC 1 is made up of α heavy chain(45KDa) and a smaller β 2 microglobulin(β​​​​​​2​​​​​​​​​​M-12 KDa).
• α​1 and α​​2 are polymorphic and variable and form the closed end peptide binding cleft.
• α​​​​​​3 is conserved and constant and interacts with CD8 marker of T cytotoxic cells.
• β2 microglobulin is a non MHC gene product which provides stability to MHC l.
• Single alpha helical transmembrane domain is present.
• 8 to 10 minute acids long antigen peptide( processed endogenous antigen)is expressed by MHC 1,C terminal end of peptide should contain hydrophobic sequences for interaction with MHC 1.

MHC class II:

• It is coded by three alleles that is HLA DP, DQ, DR
• It is made up of α chain(36 KDa) and β chain(28KDa). α​​​​​​1 and β​​​​​​1 are polymorphic and variable whereas α​​​​​​2 and β​​​​​​2 are constant and conserved.
• β​​​​​​2 interacts with CD4 molecules of T helper cells.
• α​​​​​​1 and β​​​​​​1 form the open binding cleft to which a 13 - 18 amino acid long peptide(processed exogenous antigen) interacts in which hydrophobic sequences are present throughout.
• Two membrane spanning α and β domains are present.
• MHC II is expressed by professional antigen presenting cells including macrophages B cells and dendritic cells.