Major histocompatibility complex class II-dependent antigen presentation pathway (MHC II pathway)

The Major histocompatibility complex class II-dependent antigen presentation pathway is a fundamental immunological process responsible for the presentation of exogenous antigens to CD4+ T lymphocytes [1]. This pathway begins with the endocytosis of extracellular proteins, which are then proteolytically degraded into peptides within endolysosomal compartments. Concurrently, MHC class II alpha and beta chains assemble in the endoplasmic reticulum with the invariant chain (CD74), which chaperones the complex to the endosomes [2]. Within these compartments, enzymes like Cathepsin S cleave the invariant chain, leaving the Class II-associated invariant chain peptide (CLIP) in the binding groove, which is eventually exchanged for an antigenic peptide with the help of HLA-DM [3]. The resulting MHC II-peptide complex is transported to the plasma membrane for recognition by T-cell receptors. Aberrant activity in this pathway is a hallmark of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, as well as certain malignancies and infectious diseases [4]. Pharmacological modulation of this pathway, through agents like hydroxychloroquine or cathepsin inhibitors, aims to dampen overactive immune responses or enhance anti-tumor immunity [5]. Citations: [1] Roche, P. A., & Furuta, K. (2015). The MHC class II antigen-presentation pathway. Nature Reviews Immunology, 15(4), 203-216. [2] StatPearls. (2023). Physiology, Antigen Presenting Cells. [3] Blum, J. S., et al. (2013). Pathways of antigen processing. Annual Review of Immunology, 31, 443-473. [4] Neefjes, J., et al. (2011). Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nature Reviews Immunology, 11(12), 823-836. [5] Thurmond, R. L., et al. (2005). The role of cathepsin S in inflammation and autoimmunity. Current Opinion in Investigational Drugs, 6(12), 1238-1244.

Other names

MHC class II pathwayExogenous antigen presentation pathwayMHCII processing and presentationHLA class II pathway

Modulation of the pathway occurs through inhibition of endosomal acidification, inhibition of lysosomal proteases like Cathepsin S, or direct blockade of MHC class II or invariant chain (CD74) molecules to prevent antigen presentation to CD4+ T cells [1][2].