Contact map dependence of a T-cell receptor binding repertoire
| dc.citation.articleNumber | 014406 | en_US |
| dc.citation.issueNumber | 1 | en_US |
| dc.citation.journalTitle | Physical Review E | en_US |
| dc.citation.volumeNumber | 106 | en_US |
| dc.contributor.author | Chau, Kevin Ng | en_US |
| dc.contributor.author | George, Jason T. | en_US |
| dc.contributor.author | Onuchic, José N. | en_US |
| dc.contributor.author | Lin, Xingcheng | en_US |
| dc.contributor.author | Levine, Herbert | en_US |
| dc.contributor.org | Center for Theoretical Biological Physics | en_US |
| dc.date.accessioned | 2022-09-01T14:18:19Z | en_US |
| dc.date.available | 2022-09-01T14:18:19Z | en_US |
| dc.date.issued | 2022 | en_US |
| dc.description.abstract | The T-cell arm of the adaptive immune system provides the host protection against unknown pathogens by discriminating between host and foreign material. This discriminatory capability is achieved by the creation of a repertoire of cells each carrying a T-cell receptor (TCR) specific to non-self-antigens displayed as peptides bound to the major histocompatibility complex (pMHC). The understanding of the dynamics of the adaptive immune system at a repertoire level is complex, due to both the nuanced interaction of a TCR-pMHC pair and to the number of different possible TCR-pMHC pairings, making computationally exact solutions currently unfeasible. To gain some insight into this problem, we study an affinity-based model for TCR-pMHC binding in which a crystal structure is used to generate a distance-based contact map that weights the pairwise amino acid interactions. We find that the TCR-pMHC binding energy distribution strongly depends both on the number of contacts and the repeat structure allowed by the topology of the contact map of choice; this in turn influences T-cell recognition probability during negative selection, with higher variances leading to higher survival probabilities. In addition, we quantify the degree to which neoantigens with mutations in sites with higher contacts are recognized at a higher rate. | en_US |
| dc.identifier.citation | Chau, Kevin Ng, George, Jason T., Onuchic, José N., et al.. "Contact map dependence of a T-cell receptor binding repertoire." <i>Physical Review E,</i> 106, no. 1 (2022) American Physical Society: https://doi.org/10.1103/PhysRevE.106.014406. | en_US |
| dc.identifier.digital | PhysRevE106014406 | en_US |
| dc.identifier.doi | https://doi.org/10.1103/PhysRevE.106.014406 | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/113161 | en_US |
| dc.language.iso | eng | en_US |
| dc.publisher | American Physical Society | en_US |
| dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
| dc.title | Contact map dependence of a T-cell receptor binding repertoire | en_US |
| dc.type | Journal article | en_US |
| dc.type.dcmi | Text | en_US |
| dc.type.publication | publisher version | en_US |
Files
Original bundle
1 - 1 of 1