Comparative analysis of the CDR loops of antigen receptors
The adaptive immune system uses two main types of antigen receptors: T-cell receptors (TCRs) and antibodies. While both proteins share a globally similar β-sandwich architecture, TCRs are specialised to recognise peptide antigens in the binding groove of the major histocompatibility complex, while a...
| Hauptverfasser: | , , |
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| Format: | Journal article |
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Frontiers Media
2019
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| _version_ | 1826289565621551104 |
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| author | Wong, W Leem, J Deane, C |
| author_facet | Wong, W Leem, J Deane, C |
| author_sort | Wong, W |
| collection | OXFORD |
| description | The adaptive immune system uses two main types of antigen receptors: T-cell receptors (TCRs) and antibodies. While both proteins share a globally similar β-sandwich architecture, TCRs are specialised to recognise peptide antigens in the binding groove of the major histocompatibility complex, while antibodies can bind an almost infinite range of molecules. For both proteins, the main determinants of target recognition are the complementarity-determining region (CDR) loops. Five of the six CDRs adopt a limited number of backbone conformations, known as the ′canonical classes′ ; the remaining CDR (β3 in TCRs and H3 in antibodies) is more structurally diverse. In this paper, we first update the definition of canonical forms in TCRs, build an auto-updating sequence-based prediction tool (available at http://opig.stats.ox.ac.uk/resources) and demonstrate its application on large scale sequencing studies. Given the global similarity of TCRs and antibodies, we then examine the structural similarity of their CDRs. We find that TCR and antibody CDRs tend to have different length distributions, and where they have similar lengths, they mostly occupy distinct structural spaces. In the rare cases where we found structural similarity, the underlying sequence patterns for the TCR and antibody version are different. Finally, where multiple structures have been solved for the same CDR sequence, the structural variability in TCR loops is higher than that in antibodies, suggesting TCR CDRs are more flexible. These structural differences between TCR and antibody CDRs may be important to their different biological functions. |
| first_indexed | 2024-03-07T02:30:49Z |
| format | Journal article |
| id | oxford-uuid:a72cf7ff-85f2-4048-8fa9-80d77c970ddf |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:30:49Z |
| publishDate | 2019 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:a72cf7ff-85f2-4048-8fa9-80d77c970ddf2022-03-27T02:52:41ZComparative analysis of the CDR loops of antigen receptorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a72cf7ff-85f2-4048-8fa9-80d77c970ddfSymplectic Elements at OxfordFrontiers Media2019Wong, WLeem, JDeane, CThe adaptive immune system uses two main types of antigen receptors: T-cell receptors (TCRs) and antibodies. While both proteins share a globally similar β-sandwich architecture, TCRs are specialised to recognise peptide antigens in the binding groove of the major histocompatibility complex, while antibodies can bind an almost infinite range of molecules. For both proteins, the main determinants of target recognition are the complementarity-determining region (CDR) loops. Five of the six CDRs adopt a limited number of backbone conformations, known as the ′canonical classes′ ; the remaining CDR (β3 in TCRs and H3 in antibodies) is more structurally diverse. In this paper, we first update the definition of canonical forms in TCRs, build an auto-updating sequence-based prediction tool (available at http://opig.stats.ox.ac.uk/resources) and demonstrate its application on large scale sequencing studies. Given the global similarity of TCRs and antibodies, we then examine the structural similarity of their CDRs. We find that TCR and antibody CDRs tend to have different length distributions, and where they have similar lengths, they mostly occupy distinct structural spaces. In the rare cases where we found structural similarity, the underlying sequence patterns for the TCR and antibody version are different. Finally, where multiple structures have been solved for the same CDR sequence, the structural variability in TCR loops is higher than that in antibodies, suggesting TCR CDRs are more flexible. These structural differences between TCR and antibody CDRs may be important to their different biological functions. |
| spellingShingle | Wong, W Leem, J Deane, C Comparative analysis of the CDR loops of antigen receptors |
| title | Comparative analysis of the CDR loops of antigen receptors |
| title_full | Comparative analysis of the CDR loops of antigen receptors |
| title_fullStr | Comparative analysis of the CDR loops of antigen receptors |
| title_full_unstemmed | Comparative analysis of the CDR loops of antigen receptors |
| title_short | Comparative analysis of the CDR loops of antigen receptors |
| title_sort | comparative analysis of the cdr loops of antigen receptors |
| work_keys_str_mv | AT wongw comparativeanalysisofthecdrloopsofantigenreceptors AT leemj comparativeanalysisofthecdrloopsofantigenreceptors AT deanec comparativeanalysisofthecdrloopsofantigenreceptors |