Leucine-rich repeat-containing protein 8A (LRRC8A)-derived peptide epitope presented on MHC (LRRC8A-MHC)

The Leucine-rich repeat-containing protein 8A (LRRC8A)-derived peptide epitope presented on MHC refers to a specific amino acid sequence from the LRRC8A protein, also known as SWELL1, that is processed and displayed on the cell surface by Major Histocompatibility Complex (MHC) molecules (UniProt Q8IWT6) [1]. LRRC8A is a critical component of the volume-regulated anion channel (VRAC), which plays a vital role in cellular volume homeostasis and signaling (PubMed 24703715) [2]. In several malignancies, most notably glioblastoma, LRRC8A is overexpressed, leading to the presentation of its derived peptides as tumor-associated antigens (PubMed 32433948) [3]. These peptide-MHC complexes are targeted by T-cell receptor (TCR)-engineered T-cell therapies, which aim to selectively recognize and eliminate cancer cells. However, because LRRC8A is also expressed in certain healthy tissues, such as the brain and heart, therapeutic development must address the risk of on-target, off-tumor toxicity. Current clinical and preclinical efforts focus on optimizing TCR affinity and specificity to ensure a safe and effective immune response against LRRC8A-positive tumors.

Other names

SWELL1-derived peptide epitopeLRRC8A-MHC complexLRRC8A tumor-associated antigenHLA-A*02:01 restricted LRRC8A peptide

T-cell receptor (TCR) binding to the peptide-MHC complex, leading to T-cell activation and targeted lysis of the antigen-presenting cell.