Authors :
Presenting Author: Jun Chen, PhD – Beijing Children's Hospital, Capital Medical University
Pei Zhang, PhD – Beijing Children's Hospital, Capital Medical University
Shuo pang, PhD – Beijing Children's Hospital, Capital Medical University
Guojun Zhang, PhD – Beiing Children's Hospital, Capital Medical University
Rationale:
The SCN1A gene encodes the voltage-gated sodium channel α1 subunit. Pathogenic variations of this gene can cause epileptic seizures by affecting the function of sodium channels. Patients with epilepsy associated with pathogenic SCN1A gene mutations have high clinical heterogeneity and exhibit a series of epilepsy phenotype spectra ranging from benign to severe. Neoantigens are peptides generated from somatically mutated genes that play an important role in vaccination-based immunotherapy. Neoantigens are peptides that bind to human leukocyte antigens (HLAs), computational prediction of their interaction can accelerate epitope screening and vaccine development. Currently, there are no reports of neoantigens derived from mutant SCN1A. Methods:
In this study, based on the AOMP program developed from TransPHLA, SCN1A mutant peptides are automatically optimized to find mutant peptides that have higher affinity for HLA and are highly homologous to the source peptide, generating immunogenic neoantigens for the treatment of epilepsy.Results:
The results showed that we found 15 new SCN1A mutant peptides involving 22 mutant loci, forming the Neoantigens database of SCN1A. Based on the reported X-ray crystal structure of allele-specific HLA molecules, the high-frequency allele HLA-A02:01 is selected as the target HLA molecule to verify the stable binding of neoantigens VLAIIVFIFA (derived from VLEIIVFIFA). Conclusions:
In summary, this study has identified candidate neoantigens derived from mutant SCN1A. These potential antigenic peptides can be applied to epilepsy epitope optimization or drug design, and are particularly useful for vaccine development, which possess potential immunogenicity and therapeutic potential for epilepsy.
Funding: Joint Basic-Clinical Laboratory of Pediatric Epilepsy and Cognitive Developmental, 3-1-013-03