Ephrin type-A receptor 2 peptide–Major Histocompatibility Complex (EphA2-pMHC)

The Ephrin type-A receptor 2 (EphA2) peptide–Major Histocompatibility Complex (MHC) is a specialized immunological target consisting of intracellularly processed fragments of the EphA2 protein presented on the cell surface by MHC molecules, most commonly HLA-A*02:01 (Source: PMID: 15100231). EphA2 is a receptor tyrosine kinase that is frequently overexpressed in a wide range of solid tumors, including glioblastoma, melanoma, and breast cancer, while maintaining restricted expression in normal adult tissues (Source: UniProt P29317). This differential expression pattern makes the EphA2-pMHC complex an ideal target for T-cell-based immunotherapies, such as T-cell receptor (TCR)-engineered T cells and peptide vaccines like IMA950 (Source: PMID: 25316811). These therapies work by enabling the immune system to recognize and selectively eliminate tumor cells presenting these specific peptide-MHC combinations. However, the clinical utility of targeting this complex is constrained by HLA restriction, requiring patients to possess specific MHC alleles for treatment efficacy. Additionally, potential on-target off-tumor toxicities must be carefully managed, as low-level EphA2 expression in tissues like the lung and skin could lead to adverse immune reactions (Source: PMID: 23633457). Ongoing research continues to optimize the affinity of TCRs and the composition of multi-peptide vaccines to improve therapeutic outcomes in oncology.

Other names

EphA2-pMHCEphA2-HLA-A2 complexEphA2 883-891 peptide-MHCEphrin type-A receptor 2 antigen-MHC complex

T-cell receptor binding, Peptide-based immunization, Cytotoxic T-lymphocyte activation