Quantifying conformational changes in the TCR:pMHC-I binding interface DOI Creative Commons
Benjamin McMaster, Christopher J. Thorpe,

Jamie Rossjohn

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 2, 2024

T cells form one of the key pillars adaptive immunity. Using their surface bound cell antigen receptors (TCRs), these screen millions antigens presented by major histocompatibility complex (MHC) or MHC-like molecules. In other protein families, dynamics protein-protein interactions have important implications for function. Case studies TCR:class I peptide-MHCs (pMHC-Is) structures reported mixed results on whether binding interfaces undergo conformational change during engagement and no robust statistical quantification has been done to generalise results. Thus, it remains an open question movement occurs in interface that enables recognition activation cells.

Language: Английский

The Observed T cell receptor Space database enables paired-chain repertoire mining, coherence analysis and language modelling DOI Creative Commons
Matthew I. J. Raybould, Alexander Greenshields‐Watson,

Parth Agarwal

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 21, 2024

T cell activation is governed through receptors (TCRs), heterodimers of two sequence-variable chains (often an alpha [ α ] and beta β chain) that recognise linear antigen fragments presented on the surfaces. Early sequencing technologies limited study immune repertoire TCRs to unpaired transcripts, leading extensive analysis -chain data alone as its greater sequence diversity suggested it should dominate recognition. Over time, structural has revealed both contribute binding most antigens highthroughput single-cell handling have been increasingly applied obtain samples complete TCR variable region sequences from repertoires. Despite this, there currently no repository dedicated curation publicly available paired data. We addressed this gap by creating Observed receptor Space (OTS) database, a source consistently processed annotated, full-length, paired-chain 50 studies at least 75 individuals. Currently, OTS contains 5.35M redundant (1.63M nonredundant) predominantly human and, based recent availability trends, will grow rapidly. perform initial OTS, identification pairing biases, public TCRs, distinct chain coherence patterns relative antibodies. also harness build language model, providing embedding representations method for residue in-filling conditional partner chain. be updated maintained central community resource freely downloadable web application https://opig.stats.ox.ac.uk/webapps/ots .

Language: Английский

Citations

7

The Observed T Cell Receptor Space database enables paired-chain repertoire mining, coherence analysis, and language modeling DOI Creative Commons
Matthew I. J. Raybould, Alexander Greenshields‐Watson,

Parth Agarwal

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114704 - 114704

Published: Aug. 29, 2024

T cell activation is governed through receptors (TCRs), heterodimers of two sequence-variable chains (often an α and β chain) that synergistically recognize antigen fragments presented on surfaces. Despite this, there only exist repositories dedicated to collecting single-chain, not paired-chain, TCR sequence data. We addressed this gap by creating the Observed Space (OTS) database, a source consistently processed annotated, full-length, paired-chain sequences. Currently, OTS contains 5.35 million redundant (1.63 non-redundant), predominantly human sequences from across 50 studies at least 75 individuals. Using OTS, we identify pairing biases, public TCRs, distinct chain coherence patterns relative antibodies. also release language model, providing paired embedding representations method for residue in-filling conditional partner chain. will be updated as central community resource freely downloadable available web application.

Language: Английский

Citations

4

Reading the repertoire: Progress in adaptive immune receptor analysis using machine learning DOI Creative Commons

Timothy J O'Donnell,

Chakravarthi Kanduri, Giulio Isacchini

et al.

Cell Systems, Journal Year: 2024, Volume and Issue: 15(12), P. 1168 - 1189

Published: Dec. 1, 2024

Language: Английский

Citations

2

Quantifying conformational changes in the TCR:pMHC-I binding interface DOI Creative Commons
Benjamin McMaster, Christopher J. Thorpe,

Jamie Rossjohn

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 2, 2024

T cells form one of the key pillars adaptive immunity. Using their surface bound cell antigen receptors (TCRs), these screen millions antigens presented by major histocompatibility complex (MHC) or MHC-like molecules. In other protein families, dynamics protein-protein interactions have important implications for function. Case studies TCR:class I peptide-MHCs (pMHC-Is) structures reported mixed results on whether binding interfaces undergo conformational change during engagement and no robust statistical quantification has been done to generalise results. Thus, it remains an open question movement occurs in interface that enables recognition activation cells.

Language: Английский

Citations

1