ArticleScientific reports2024
Broadening alloselectivity of T cell receptors by structure guided engineering.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- MHCXGraph: a graph-based approach to detecting T-cell receptor cross-reactivity.Briefings in bioinformatics · 2026Article
- Dual-degenerate TCRs target multiple KRAS hotspot and HLA-A3 family combinations.Research square · 2026Article
- A generalizable system for antigenic peptide targeting across HLA-I allotypes.bioRxiv : the preprint server for biology · 2026Article
- Safety and biologic activity of a bispecific T cell receptor targeting HIV Gag in males living with HIV: a first-in-human trial.Nature communications · 2026Article
- Quantitative and large-scale investigation of human TCR-HLA cross-reactivity.Science advances · 2025Article
- Adoptive T-Cell Therapy in Sarcomas.Current oncology reports · 2025Review
- A structure-guided approach to predict MHC-I restriction of T cell receptors for public antigens.Structure (London, England : 1993) · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
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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.
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Registered trials
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