Major Histocompatibility Complex class I and II antigen presentation machinery (MHC I/II APM)

The Major Histocompatibility Complex (MHC) class I and II antigen presentation machinery is a multi-component system essential for the adaptive immune system's ability to recognize pathogens and malignant cells. MHC class I molecules, found on almost all nucleated cells, present endogenous peptides to CD8+ cytotoxic T cells, while MHC class II molecules are expressed on professional antigen-presenting cells (APCs) to present exogenous peptides to CD4+ helper T cells (StatPearls, 2023). This machinery encompasses the MHC proteins themselves, the proteasome, transporters associated with antigen processing (TAP), and various chaperones like tapasin and the invariant chain (CD74) (Janeway's Immunobiology, 9th ed.). In many cancers, components of this machinery are downregulated or mutated to facilitate immune evasion, a process known as 'immune coldness' (Nature Reviews Cancer, 2020). Therapeutic strategies often aim to upregulate this machinery using interferons, HDAC inhibitors, or certain kinase inhibitors to restore T-cell recognition and enhance the efficacy of checkpoint inhibitors (PubMed, PMID: 30241496). Conversely, in autoimmunity and transplantation, the machinery is a target for suppression to prevent unwanted immune attacks on self-tissues or grafts.

Other names

Human Leukocyte Antigen systemHLA class I and IIAntigen processing and presentation pathwayMHC-I and MHC-II machineryMHC-peptide signaling complex

Modulation of MHC gene transcription via CIITA or NF-kappaB pathways, enhancement of proteasomal processing, stabilization of the peptide-loading complex, and increased surface translocation of MHC-peptide complexes.