Question

T cells have to work in a partnership with an Antigen Presenting Cell (APC). Before this can occur, the APC must modify the antigen. Please discuss how this process happens and the major protein that is involved. Be detailed

Answer 1

T cells have to work in a partnership with an Antigen Presenting Cell (APC). Before this can occur, the APC must modify the antigen. This process is occur in a pathway called exogenous pathway . I described the pathway in detailed.

Explanation of exogenous pathway of antigen processing and presentation.
Exogenous pathway of antigen processing and presentation occur in APCs( antigen presenting cells). some of the most common APVCs are monocytes ,macrophages dendritic cells found in any external receptor directly contact with external environment , kupffer cells of liver , intraglomemerular mesengial cells of kidney, alveolar macrophages of lungs, mast cell of connective tissue ,microglia of brain and so many.

APC internalizes exogenous antigen particle by phagocytosis or endocytosis or pinocytosis. Phagocytosis done by either forming pseudopods by receptor mediating way.
After internalization, the antigen closed into in endosomal vesicle with proper maintained pH . The antigen encounter stepwise many endosomal component with increasing acidic environments. The components are —Early endosome ( pH 6--6.5), late endosomes or endolysosomes( pH 4.5-5) and lysosomes( pH 4.5). With this increasing acidic pH the antigens encounter many hydrolytic enzymes which optimally active under acidic condition (low pH). These hydrolytic enzyme cuts the antigenic substances into small peptide about 13 to 18 residue which is suitable for MHC class II antigen binding groove.

on the other hand MHCclass II alpha and beta chain synthesized in the Rough Endoplasmic Reticulum(RER) and entered into endoplasmic reticulum where they associated with a protein called invariant chain(li). This protein prevent the binding of any endogenous peptide to the antigen binding groove of MHC class II molecule and also involved in proper folding of alpha and beta chain of class II MHC molecule.Then MHC class II molecule associated with invariant chain exit from endoplasmic reticulum and entered into Golgi complex and then formed in the endocytic compartment.

Then MHC class II molecule interact with antigenic peptide in the late endosome(pH 4.5-5) which is known as MHC class II containing compartment ( MIIC). Due to proteolytic activity of the enzymes present in the compartments invariant chain gradually decreased and form a short fragment called as CLIP( Class II associated invarient chain peptide) .

CLIP is replaced with antigenic peptide by a non classical class II MHC molecule called HLA -DM. HLA-DM associate with class II beta chain and function in removing of CLIP and binding of antigenic peptide. Another non classical MHC class II family HLA-DO act as a negative regulator of antigen binding to the binding cleft.

Once peptide has bound, it formed lysosome (pH 4.5)and transported to cell membrane and expressed in the cell surface.In the cell surface it present antigen to CD4 + helper T - lymphocytes .