Human leukocyte antigen class I antigen presentation pathway (HLA-I pathway)

The HLA class I antigen presentation pathway is a fundamental immunological process responsible for displaying intracellular peptide fragments on the cell surface for surveillance by CD8+ cytotoxic T lymphocytes [1, 3]. This pathway involves the degradation of endogenous proteins by the proteasome, the transport of resulting peptides into the endoplasmic reticulum by the Transporter associated with Antigen Processing (TAP), and the loading of these peptides onto HLA class I molecules with the help of a peptide-loading complex [2, 4]. By presenting a snapshot of the cell's internal protein environment, the pathway allows the immune system to identify and eliminate cells that are virally infected or malignantly transformed [1, 13]. In many cancers, this pathway is frequently downregulated or mutated (e.g., loss of B2M or TAP), allowing tumor cells to evade immune detection and resist T-cell-based therapies [11, 17]. Conversely, certain autoimmune diseases are strongly associated with specific HLA class I alleles that may inappropriately present self-peptides [10, 14]. Therapeutic strategies often aim to restore or enhance this pathway using interferon-gamma, epigenetic modulators, or targeted kinase inhibitors to improve the efficacy of immune checkpoint inhibitors and vaccines [6, 11, 17].

Other names

MHC class I antigen processing and presentation pathwayEndogenous antigen presentation pathwayHLA class I antigen processing machineryHLA-I APMMHC-I pathway

Modulation of proteasomal degradation, enhancement of peptide transport via TAP, upregulation of HLA class I surface expression, and stabilization of the peptide-loading complex.