Human leukocyte antigen (HLA) class I and class II molecules (HLA-I/II)

Human leukocyte antigen (HLA) molecules, the human version of the major histocompatibility complex (MHC), are essential cell surface glycoproteins that play a central role in the adaptive immune system. MHC class I molecules are expressed on nearly all nucleated cells and present endogenous peptides to CD8+ cytotoxic T-cells, while MHC class II molecules are primarily found on professional antigen-presenting cells and present exogenous peptides to CD4+ helper T-cells (UniProt, 2024; Wikipedia, 2024). These molecules are critical for the recognition of foreign pathogens and the maintenance of self-tolerance. In disease states, HLA polymorphisms are strongly associated with susceptibility to numerous autoimmune disorders, and the loss of MHC expression is a common mechanism by which cancer cells evade immune detection (PubMed, 2023). Therapeutically, MHC molecules are targeted indirectly through immunosuppressants that block T-cell signaling or directly through biologics designed to interfere with antigen presentation or costimulation. Understanding HLA compatibility is also the cornerstone of successful organ and hematopoietic stem cell transplantation to prevent rejection (NIH, 2024).

Other names

Major histocompatibility complex (MHC)Human leukocyte antigen complexMHC class I and class IIHLA-A/B/C and HLA-DP/DQ/DR

Drugs targeting or interacting with MHC molecules typically work by modulating the presentation of antigens to T-cells, inhibiting the costimulatory signals required for T-cell activation, or masking the MHC molecule to prevent immune recognition in transplantation and autoimmune contexts (StatPearls, 2023; NIH, 2024).