T-cell receptor recognizing AE37-MHC class II complex (AE37-TCR)

The CD4+ T-cell receptor recognizing the AE37-MHC class II complex is a specialized immunological receptor that plays a pivotal role in the adaptive immune response against HER2/neu-expressing tumors. AE37 is a hybrid peptide vaccine comprising the HER2/neu-derived peptide AE36 (residues 776–790) and the Ii-Key (LRMK) sequence, which enhances the potency of the peptide by facilitating direct loading into the MHC class II binding groove (Perez et al., 2010, Clin Cancer Res). This specific T-cell receptor (TCR) identifies the AE37 peptide when presented by Major Histocompatibility Complex (MHC) class II molecules, primarily HLA-DR, on the surface of antigen-presenting cells. Upon recognition, the TCR triggers the activation and expansion of CD4+ helper T cells, which are essential for orchestrating a robust anti-tumor response through the secretion of cytokines like interferon-gamma and the recruitment of CD8+ cytotoxic T cells (Mittendorf et al., 2016, Ann Oncol). Clinically, this interaction is targeted to prevent recurrence in patients with HER2-positive cancers, such as breast and prostate cancer, following standard-of-care treatments. The therapeutic efficacy of targeting this TCR is often monitored via delayed-type hypersensitivity (DTH) skin tests and immunological assays measuring T-cell proliferation and cytokine production (Holmes et al., 2011, J Clin Oncol). While generally safe, the primary challenges include ensuring sufficient HLA-DR compatibility and managing mild systemic immune-related adverse effects.

Other names

HER2/neu (776-790) specific T-cell receptorIi-Key/HER2/neu peptide-specific TCRAE37-specific CD4+ T-cell receptorT-cell receptor recognizing Ii-Key/HER2/neu (776-790) hybrid peptide

The AE37 peptide vaccine acts as an agonist for the T-cell receptor by being presented on MHC class II molecules. The Ii-Key modification (LRMK) on the peptide enhances its loading into the MHC class II binding groove of antigen-presenting cells, allowing the TCR to recognize the complex and trigger CD4+ T-cell activation, which coordinates a broader anti-tumor immune response.