Human epidermal growth factor receptor 2 (HER2) peptide-major histocompatibility complex II (MHC II) (HER2-MHC II)

Human epidermal growth factor receptor 2 (HER2) peptide-MHC II complexes are molecular assemblies consisting of a processed peptide fragment from the HER2 protein bound to a Major Histocompatibility Complex Class II (MHC II) molecule (UniProt P04626). These complexes are primarily expressed on the surface of professional antigen-presenting cells or tumor cells, where they serve as the specific ligand for the T-cell receptor (TCR) of CD4+ helper T cells (PMID: 15155834). Recognition of these complexes by CD4+ T cells is a critical step in orchestrating an effective anti-tumor immune response, as it triggers the secretion of pro-inflammatory cytokines like interferon-gamma and provides necessary help for the activation and persistence of CD8+ cytotoxic T cells (PMID: 22532582). In many cancers, such as breast and gastric carcinomas, HER2 is overexpressed, making these peptide-MHC complexes attractive targets for immunotherapy (PMID: 11544365). Therapeutic strategies include peptide-based vaccines like AE37, designed to expand the endogenous HER2-specific CD4+ T cell population, and adoptive cell therapies using TCR-engineered T cells (PMID: 24501013). However, challenges remain regarding the heterogeneity of HLA alleles across the population and the potential for immune evasion through the downregulation of MHC molecules by tumor cells.

Other names

ERBB2 peptide-MHC II complexHER2/neu peptide-HLA class II complexHER2-MHC class II complexHER2-HLA-DR complex

Activation of HER2-specific CD4+ helper T cells to coordinate anti-tumor immunity and enhance CD8+ T cell effector function.