Antigen presentation in the immune system involves the processing of antigen, association of processed antigen with MHC molecules and cell surface presentation of the antigen in the context of MHC to T cells. This process is central to the development of innate and adaptive immunity. The pathway associated with antigen processing and presentation depends on the nature of the antigen- whether it is intracellular or extracellular in origin. MHC class I molecules present degradation products derived from intracellular (endogenous) proteins in the cytosol. MHC class II molecules present fragments derived from extracellular (exogenous) proteins that are located in an intracellular compartment.
Intracellular proteins typically intracellular or viral proteins are processed by a proteasome whose members include large multifunctional peptidase 2 (LMP2) and LMP7. The peptides are translocated into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). A transient complex containing a class I heavy chain-beta 2 microglobulin dimer is assembled onto the TAP molecule aided by ER chaperones calnexin and calreticulin and the peptide editor tapasin. The peptide loaded Class I MHC dimer is transported to the Golgi network, where the peptide undergoes further processing. This is followed by cell surface expression of the mature processed antigen in the context of Class I MHC protein to CD+8 T cells.
Extracellular antigens like bacteria are typically endocytosed by antigen presenting cells like macrophages and denditic cell. The antigen processed undergoes proteolytic degradation in the late endosomal compartment. Nascent Class II MHC proteins that are synthesized in the ER are associated with a Class II MHC associated Invariant peptide (CLIP). These newly synthesized Class II molecules undergo further maturation in the Golgi compartment, after which they transect the endocytic pathway. The invariant peptide dissociates from the Class II MHC protein in the late endosomal compartment following which binding of the fragmented antigen is facilitated. The complex of Class II MHC protein and peptide is then transported to the cell surface, where antigen presentation to CD+4 T cells occurs.
This pathway highlights the molecular events that lead to the presentation of extracellular and intracellular antigens to CD+4 and CD+8 T cells respectively.