Exogenous pathogen of antigen processing and presentation
Exogenous antigen are processed by the endosomal processing pathway. Exogenous antigens such as bacteria , viral , protozoa , fungal and parasitic antigens are delivered from outside the body antigen presenting cells (APCs) internalize antigens by phagocytosis or endocytosin . The internalize is followed sequential steps and finally the processed peptide is presented on class2 MHC on the surface of APCs , which then activates the CD4+ TH cells.
The pathway involves the following
steps-
1. Processing of antigen into peptides in endocytic vesicles-
The endocytic pathway involves the acidic components with hydrolytic enzymes with varying pH such as early endosome (pH 6.0-6.5) , late endosome (pH 5.0 – 6.0 ) and lysome (pH 4.5 – 5.0) and contains hydrolases like nuclease , proteins , phospholipids, lipases, prosphalates end glycosin.
Intelized exogenous antigen first moves into early endosome , then into late endosome and finally into lysosomes encounting hydrolytic enzymes . Increased acidity activates hydrolytic protease enzymes that cleave the protein antigen into small peptides of 13-18 amino acid residues long.
2 . Transport of class 3 MHC molecules to endocytic vesicles
Class 2 MHC alpha and bita chains are synthesized on the polysomes of rough endoiplasmic reticulum (RER) and transported into RER lumen where it gets associated with protein shown RER lumen where it gets associated with a protein lhown as invariant chain . Invariant chain involves in proper folding of class 2 MHC alpha and Bita chains and their exit from RER to golgi complex , then through specialized vesicles to the early endosomes , to late endosome and finally into lysosomes . Except a small fragment of invariant chain known as CIIP to the antigen binding clefe of class 2 MHC , the remaining part of the chain is degraded completely within the highly acidic compartment of lysosomes.
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3. Assembly of peptide with class 2 MHC
CLIP prevents premature binding of peptides to MHC class 2 molecules . A non classical MHC class2 molecules called MHC. DM, removes CLIP from the peptide binding claze and helps to load the antigenic peptide into the groove . The peptide loaded class 2 MHC – Pmhc is transported into membrane vesicles to the plasma membrane. The membrane of transport vesicle fuse with the cell membrane and PMHC complex bind to the membrane and displayed at the cell lengae .
It is presented to The cells with appropriate TCR and CD4 molecules.