Oncofetal antigen-derived peptide–MHC class I complex (OFA-pMHC I)

The Oncofetal antigen-derived peptide–MHC class I complex is a specialized molecular assembly consisting of a peptide fragment from the oncofetal antigen (OFA), also known as the immature laminin receptor protein (iLRP), bound to a Major Histocompatibility Complex (MHC) class I molecule. OFA/iLRP is a highly conserved protein that is significantly overexpressed in a wide range of hematologic malignancies and solid tumors, such as acute myeloid leukemia and breast cancer, while its expression is restricted in normal adult tissues (Siegel et al., 2003, Blood; Rohrer et al., 2006, J. Immunol.). On the surface of antigen-presenting cells (APCs) or tumor cells, this complex serves as a critical ligand for the T-cell receptor (TCR) of CD8+ cytotoxic T-lymphocytes (CTLs). Recognition of the OFA-pMHC I complex by CTLs triggers an immune response aimed at eliminating cells that display the antigen (Coggin et al., 1999, Anticancer Res.). This complex is a primary target for cancer vaccines, including dendritic cell-based therapies where APCs are pulsed with OFA peptides to prime the immune system against the tumor. Therapeutic development focuses on maximizing the specificity of TCR binding to avoid off-target effects on healthy tissues that might express trace amounts of the protein. Consequently, the OFA-pMHC I complex represents a promising focal point for personalized immunotherapy and the development of TCR-engineered T-cell products.

Other names

OFA/iLRP peptide-MHC complexImmature laminin receptor protein peptide-HLA complex37-kDa laminin receptor precursor peptide-MHCOFA-pMHC complexiLRP-derived peptide-MHC class I

Activation of antigen-specific CD8+ T-cells through T-cell receptor (TCR) recognition of the peptide-MHC complex, leading to the release of perforins and granzymes and subsequent tumor cell lysis.