Antigen presentation pathway (APP) (APP)

The antigen presentation pathway is a fundamental immunological process by which cells display peptide fragments of proteins on their surface via Major Histocompatibility Complex (MHC) molecules for recognition by T-cells (Janeway et al., 2001). This system is divided into the endogenous pathway (MHC Class I), which presents intracellular antigens to CD8+ cytotoxic T-cells, and the exogenous pathway (MHC Class II), which presents extracellular antigens to CD4+ helper T-cells (Nature Reviews Immunology, 2019). It serves as the critical link between innate and adaptive immunity, ensuring the detection of pathogens and malignant cells (NIH, 2023). In many cancers, this pathway is downregulated through the loss of MHC or TAP proteins to evade immune surveillance, while in autoimmune diseases, it may inappropriately present self-antigens (PubMed, 2021). Therapeutic strategies include proteasome inhibitors like Bortezomib that modulate peptide supply and vaccines designed to optimize antigen loading and presentation (StatPearls, 2023). Additionally, checkpoint inhibitors rely on the functional integrity of this pathway to ensure that T-cells can recognize the tumor antigens being presented (Cell, 2020).

Other names

Antigen processing and presentationMHC-mediated antigen presentationEndogenous antigen presentation pathwayExogenous antigen presentation pathwayCross-presentation

Drugs modulate this pathway by inhibiting the 26S proteasome to prevent the generation of antigenic peptides, altering endosomal pH to disrupt MHC Class II peptide loading, or utilizing cytokines to transcriptionally upregulate MHC molecules and transporter proteins.