Major Histocompatibility Complex class I peptide-loading pathway (MHC I PLP) (MHC I PLP)

The Major Histocompatibility Complex (MHC) class I peptide-loading pathway is a fundamental cellular process responsible for presenting intracellular antigens to CD8+ T cells [PMID: 21217761]. This pathway involves the degradation of proteins by the proteasome, the transport of peptides into the endoplasmic reticulum (ER) via the Transporter associated with Antigen Processing (TAP), and the assembly of the peptide-loading complex (PLC) [UniProt: P33527]. The PLC, which includes tapasin, calreticulin, and ERp57, facilitates the loading of high-affinity peptides onto MHC class I molecules [UniProt: O15520]. Once loaded, the MHC-peptide complexes are transported to the cell surface for recognition by the immune system. In many cancers, components of this pathway are downregulated to evade immune detection, a process known as 'immune escape' [PMID: 25361612]. Conversely, drugs like proteasome inhibitors (e.g., bortezomib) modulate this pathway by altering the pool of available peptides, primarily used in treating multiple myeloma [FDA Label: Bortezomib]. Therapeutic strategies also include using interferons to upregulate pathway components and enhance tumor immunogenicity.

Other names

MHC class I antigen presentation pathwayMHC I processing and presentationClass I MHC peptide loading complex pathwayMHC I antigen processing pathway

Inhibition of the 26S proteasome to prevent the generation of antigenic peptides; induction of pathway component expression via JAK-STAT signaling.