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

Human leukocyte antigen (HLA) class I and class II molecules are critical components of the adaptive immune system, encoded by the major histocompatibility complex (MHC) on chromosome 6. HLA class I molecules (HLA-A, -B, -C) are expressed on almost all nucleated cells and present endogenous peptides to CD8+ cytotoxic T cells, while HLA class II molecules (HLA-DR, -DP, -DQ) are primarily found on professional antigen-presenting cells and present exogenous peptides to CD4+ helper T cells (UniProt, 2024; Wikipedia, 2024). These proteins play a fundamental role in distinguishing self from non-self, making them central to the pathogenesis of autoimmune disorders, infectious diseases, and the success of organ and hematopoietic stem cell transplantation. In therapeutic contexts, HLA molecules are targeted indirectly through immunosuppressants that block T-cell activation or directly through strategies aimed at desensitizing patients with pre-existing anti-HLA antibodies. Understanding HLA polymorphism is also vital for personalized medicine, as specific alleles are strongly associated with drug hypersensitivity reactions and disease susceptibility (PubMed, 2023; NIH, 2024).

Other names

Major histocompatibility complexMHC class I and IIHLA antigensHuman leukocyte antigen system

Drugs targeting or interacting with HLA molecules typically function by inhibiting T-cell costimulation, suppressing the overall immune response to prevent graft rejection, or enzymatically cleaving IgG antibodies that would otherwise bind to HLA antigens in sensitized patients (StatPearls, 2023; NIH, 2024).