Peptide-Major Histocompatibility Complex class II (pMHCII) complex (pMHCII)

The peptide-Major Histocompatibility Complex class II (pMHCII) complex is a molecular assembly consisting of a heterodimeric MHC class II molecule (HLA-DR, -DQ, or -DP in humans) and a bound antigenic peptide, typically 13-25 amino acids in length. Primarily expressed on professional antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells, these complexes present exogenous antigens to CD4+ T-helper cells to initiate and orchestrate adaptive immune responses. In oncology, tumor cells can aberrantly express MHC II, presenting tumor-associated antigens or neoantigens that serve as highly specific targets for TCR-like antibodies, bispecific engagers, and CAR-T therapies. Conversely, in autoimmune diseases, the presentation of self-peptides by specific MHC II alleles triggers pathogenic immune responses, making the complex a target for inhibitory therapies like glatiramer acetate. Therapeutic strategies focus on either leveraging the complex to direct immune-mediated destruction of malignant cells or blocking the complex to restore immune tolerance in autoimmune conditions.

Other names

HLA class II-peptide complexMHC II-peptide complexpMHCIITumor-specific MHC-II (tsMHC-II)Antigen-MHC class II complex

Binding to the specific peptide-MHC complex to either trigger immune-mediated cell killing (in cancer) or inhibit pathogenic T-cell activation (in autoimmunity).