Antigen-presenting cell receptors and processing pathways

Antigen-presenting cell (APC) receptors and processing pathways represent the integrated system by which specialized immune cells, such as dendritic cells and macrophages, internalize, degrade, and display antigenic peptides to T lymphocytes [1]. This process begins with antigen capture via pattern recognition receptors (PRRs) or endocytic receptors, followed by proteolytic cleavage in the proteasome for MHC class I or endosomes for MHC class II [2][3]. The resulting peptides are then loaded onto Major Histocompatibility Complex (MHC) molecules and transported to the cell surface for recognition by T-cell receptors (TCRs) [4]. This pathway is critical for the induction of adaptive immunity against pathogens and tumors, as well as the maintenance of peripheral tolerance [3]. In oncology, tumors often downregulate components of this pathway, such as TAP transporters or MHC expression, to evade immune surveillance [5]. Conversely, in autoimmune disorders, the pathway may be hyperactive or misdirected against self-antigens, leading to tissue destruction [4]. Pharmacological intervention includes proteasome inhibitors like bortezomib to alter the peptide repertoire and checkpoint inhibitors that modulate the costimulatory signals provided by APCs during presentation [6]. Understanding these pathways is essential for developing vaccines and immunotherapies that can precisely tune the immune response [1]. Sources: [1] Roche PA, Furuta K. Nat Rev Immunol. 2015;15(4):203-16. [2] Blum JS, et al. Annu Rev Immunol. 2013;31:443-73. [3] StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. [4] Gaudino SJ, Kumar P. Ref Mod Biomed Sci. 2019. [5] Leone P, et al. J Natl Cancer Inst. 2013;105(16):1172-87. [6] PubChem Compound Summary for CID 387447 (Bortezomib).

Other names

Antigen presentation machineryAntigen processing and presentation (APP) pathwayMHC processing and presentationAPC signaling pathways

Drugs targeting these pathways function by inhibiting the proteasomal degradation of proteins into peptides, blocking costimulatory signals between APCs and T cells, or preventing inhibitory checkpoint interactions to restore or suppress immune activity.