HLA-A*02:01-presented Low-density lipoprotein receptor-related protein-associated protein 1 (21-30) epitope (HLA-A2/LRPAP1(21-30))

The HLA-A*02:01-presented LRPAP1 (21-30) epitope is a T-cell epitope associated with impaired peptide processing (TEIPP), specifically the peptide ALWAGLALLL derived from the signal sequence of the Low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) (Van Hall et al., 2006). In normal cells, the Transporter associated with Antigen Processing (TAP) complex loads MHC Class I molecules with cytosolic peptides; however, many tumors downregulate TAP to evade immune detection (Doorn et al., 2021). In these TAP-deficient cells, HLA-A*02:01 molecules are loaded with alternative peptides, such as the LRPAP1 signal sequence, which enter the endoplasmic reticulum via the Sec61 translocon (Lampen et al., 2010). This epitope serves as a unique target for immunotherapy, allowing for the selective recognition and destruction of immune-evasive, TAP-deficient tumor cells while sparing healthy TAP-proficient tissues. Current therapeutic development focuses on TCR-engineered T cells and TCR-like antibodies that can specifically bind this peptide-MHC complex to restore anti-tumor immunity in advanced cancers (Marijt et al., 2018).

Other names

LRPAP1 signal peptide epitopeTEIPP-LRPAP1HLA-A*02:01/ALWAGLALLLLRPAP1_21-30

T-cell mediated cytotoxicity against TAP-deficient cells