ArticleProtein science : a publication of the Protein Society2006
Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without increasing apparent cross-reactivity.
Article in Protein science : a publication of the Protein Society, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 110 citations in OpenAlex.
- Structural T-Cell Receptor Analysis in the Age of Machine Learning.Immunological reviews · 2026Review
- Computational design of orthogonal TCR α/β interfaces for dual-TCR therapeutics.bioRxiv : the preprint server for biology · 2026Article
- ImmTAC: A Novel Platform of T-Cell Receptor-Based Soluble Bispecifics.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Avidity-optimized TCR-T cells target KRAS neoantigens for potent cancer clearance and tumor microenvironment remodeling.Frontiers in immunology · 2026Article
- Development of DARPin T cell engagers for specific targeting of tumor-associated HLA/peptide complexes.iScience · 2025Article
- T cell receptor specificity landscape revealed through de novo peptide design.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- T-cell receptor specificity landscape revealed through de novo peptide design.bioRxiv : the preprint server for biology · 2025Article
- Phage display enables machine learning discovery of cancer antigen-specific TCRs.Science advances · 2025Article
- Preclinical model for evaluating human TCRs against chimeric syngeneic tumors.Journal for immunotherapy of cancer · 2024Article
- Broadening alloselectivity of T cell receptors by structure guided engineering.Scientific reports · 2024Article
- Exploring the potential of structure-based deep learning approaches for T cell receptor design.PLoS computational biology · 2024Article
- Identification and affinity enhancement of T-cell receptor targeting a KRASCommunications biology · 2024Article
- Exploring the Potential of Structure-Based Deep Learning Approaches for T cell Receptor Design.bioRxiv : the preprint server for biology · 2024Article
- Enhanced T cell receptor specificity through framework engineering.Frontiers in immunology · 2024Article
- Challenges and solutions for therapeutic TCR-based agents.Immunological reviews · 2023Review
- Therapeutic high affinity T cell receptor targeting a KRASNature communications · 2022Article
- Combination strategies to durably suppress HIV-1: Soluble T cell receptors.Journal of virus eradication · 2022Article
- Engineering the T cell receptor for fun and profit: Uncovering complex biology, interrogating the immune system, and targeting disease.Current opinion in structural biology · 2022Review
- Rapid screening of TCR-pMHC interactions by the YAMTAD system.Cell discovery · 2022Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian alpha/beta T cell receptor (TCR) repertoire plays a pivotal role in adaptive immunity by recognizing short, processed, peptide antigens bound in the context of a highly diverse family of cell-surface major histocompatibility complexes (pMHCs). Despite the extensive TCR-MHC interaction surface, peptide-independent cross-reactivity of native TCRs is generally avoided through cell-mediated selection of molecules with low inherent affinity for MHC. Here we show that, contrary to expectations, the germ line-encoded complementarity determining regions (CDRs) of human TCRs, namely the CDR2s, which appear to contact only the MHC surface and not the bound peptide, can be engineered to yield soluble low nanomolar affinity ligands that retain a surprisingly high degree of specificity for the cognate pMHC target. Structural investigation of one such CDR2 mutant implicates shape complementarity of the mutant CDR2 contact interfaces as being a key determinant of the increased affinity. Our results suggest that manipulation of germ line CDR2 loops may provide a useful route to the production of high-affinity TCRs with therapeutic and diagnostic potential.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.