8RYP

Structure of S8 TCR in complex with HLA-A*03:01 bound to ELFSYLIEK peptide

8RYP の概要

• エントリーDOI: 10.2210/pdb8ryp/pdb
• 分子名称: HLA class I histocompatibility antigen, A alpha chain, Beta-2-microglobulin, ELFSYLIEK peptide, ... (7 entities in total)
• 機能のキーワード: tcr, hla, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 94274.51

構造登録者

Karuppiah, V. (登録日: 2024-02-09, 公開日: 2024-09-04, 最終更新日: 2025-02-12)

主引用文献

Karuppiah, V.,Sangani, D.,Whaley, L.,Pengelly, R.,Uluocak, P.,Carreira, R.J.,Hock, M.,Cristina, P.D.,Bartasun, P.,Dobrinic, P.,Smith, N.,Barnbrook, K.,Robinson, R.A.,Harper, S.
Broadening alloselectivity of T cell receptors by structure guided engineering.
Sci Rep, 14:26851-26851, 2024

PubMed Abstract: Specificity of a T cell receptor (TCR) is determined by the combination of its interactions to the peptide and human leukocyte antigen (HLA). TCR-based therapeutic molecules have to date targeted a single peptide in the context of a single HLA allele. Some peptides are presented on multiple HLA alleles, and by engineering TCRs for specific recognition of more than one allele, there is potential to expand the targetable patient population. Here, as a proof of concept, we studied two TCRs, S2 and S8, binding to the PRAME peptide antigen (ELFSYLIEK) presented by HLA alleles HLA-A*03:01 and HLA-A*11:01. By structure-guided affinity maturation targeting a specific residue on the HLA surface, we show that the affinity of the TCR can be modulated for different alleles. Using a combination of affinity maturation and functional T cell assay, we demonstrate that an engineered TCR can target the same peptide on two different HLA alleles with similar affinity and potency. This work highlights the importance of engineering alloselectivity for designing TCR based therapeutics suitable for differing global populations.

PubMed: 39500929
DOI: 10.1038/s41598-024-75140-7

実験手法

X-RAY DIFFRACTION (1.81 Å)