Peptide-Human Leukocyte Antigen class II complex (pHLA-II)

Peptide-Human Leukocyte Antigen (HLA) class II complexes are heterotrimeric structures composed of an alpha chain, a beta chain, and a bound proteolytic peptide fragment, typically 13 to 25 amino acids in length [Murphy K, Weaver C. Janeway's Immunobiology. 9th ed. Garland Science; 2016]. While HLA class I molecules are ubiquitously expressed, HLA class II expression is primarily restricted to professional antigen-presenting cells of the hematopoietic system, such as B cells, dendritic cells, and macrophages, as well as certain malignant cells in leukemia and lymphoma [Alstein et al. Nature Communications, 2021]. These complexes function by presenting endogenous or exogenous antigens to the T-cell receptors (TCRs) of CD4+ T helper cells, which is a critical step in orchestrating the adaptive immune response. In hematological malignancies like acute myeloid leukemia (AML), these complexes can present tumor-associated antigens or neoantigens, making them highly specific targets for advanced immunotherapies [He et al. Journal of Hematology & Oncology, 2019]. Therapeutic strategies, such as TCR-engineered T cells (TCR-T) and TCR-like antibodies, are designed to recognize the unique molecular surface formed by the specific peptide-HLA interface [Rock et al. Chemical Reviews, 2016]. However, the high degree of HLA polymorphism requires precise patient-specific HLA matching, and a major safety concern remains the potential for off-target toxicity if the targeted peptide sequence mimics proteins found in vital organs [Yao et al. Journal of Clinical Investigation, 2016].

Other names

MHC class II-peptide complexpMHCIIHLA class II-peptide complexPeptide-HLA-DR complexPeptide-HLA-DQ complexPeptide-HLA-DP complex

Recognition of specific peptide-HLA complexes by engineered receptors (TCRs or antibodies) to trigger T-cell mediated cytotoxicity or immune modulation against cells presenting the target antigen.