Human leukocyte antigen class II complex (HLA-II)

Human leukocyte antigen class II (HLA-II) complexes are heterodimeric cell surface glycoproteins that play a fundamental role in the adaptive immune system by presenting processed antigenic peptides to CD4+ T cells (UniProt, 2024). While HLA-II is constitutively expressed on professional antigen-presenting cells, it can be aberrantly induced on non-hematopoietic host tissues, such as intestinal epithelial cells, skin keratinocytes, and biliary epithelium, primarily through interferon-gamma (IFN-γ) signaling (Koyama et al., Nature, 2012). In the context of graft-versus-host disease (GvHD), these peptide-HLA-II complexes on non-hematopoietic tissues serve as primary targets for donor-derived CD4+ T cells, initiating a cascade of inflammatory damage and tissue destruction (Markey et al., JCI, 2014). This tissue-specific expression is now recognized as a critical driver of lethal GvHD, independent of HLA-II expression on hematopoietic cells (Koyama et al., Blood, 2015). Therapeutic strategies targeting this complex include JAK inhibitors like Ruxolitinib, which suppress IFN-γ-mediated HLA-II upregulation, and co-stimulation blockers like Abatacept, which prevent the activation of T cells recognizing these complexes (Zeiser & Blazar, NEJM, 2017). Monitoring HLA-DR expression in tissue biopsies serves as a potential biomarker for disease severity and therapeutic response in GvHD patients (PubMed, 2023).

Other names

MHC class IIMajor histocompatibility complex class IIHLA-DRHLA-DQHLA-DPPeptide-MHC II complexHLA class II antigen

Inhibition of T-cell receptor (TCR) signaling, blockade of CD28-mediated co-stimulatory signals, and suppression of HLA-II expression on target tissues via JAK/STAT pathway inhibition.