Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals
Recent advances in high-throughput T cell receptor (TCR) sequencing have allowed for new insights into the human TCR repertoire. However, methods for capturing antigen-specific repertoires remain an area of development. Here, we describe a potentially novel approach that utilizes both a biological a...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2021
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| Online Access: | https://hdl.handle.net/1721.1/135626 |
| _version_ | 1811090547090128896 |
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| author | Smith, Neal P Ruiter, Bert Virkud, Yamini V Tu, Ang A Monian, Brinda Moon, James J Love, J Christopher Shreffler, Wayne G |
| author2 | Massachusetts Institute of Technology. Department of Physics |
| author_facet | Massachusetts Institute of Technology. Department of Physics Smith, Neal P Ruiter, Bert Virkud, Yamini V Tu, Ang A Monian, Brinda Moon, James J Love, J Christopher Shreffler, Wayne G |
| author_sort | Smith, Neal P |
| collection | MIT |
| description | Recent advances in high-throughput T cell receptor (TCR) sequencing have allowed for new insights into the human TCR repertoire. However, methods for capturing antigen-specific repertoires remain an area of development. Here, we describe a potentially novel approach that utilizes both a biological and statistical enrichment to define putatively antigen-specific complementarity-determining region 3 (CDR3) repertoires in unselected individuals. The biological enrichment entailed FACS of in vitro antigen-activated memory CD4+ T cells, followed by TCRβ sequencing. The resulting TCRβ sequences were then filtered by selecting those that are statistically enriched when compared with their frequency in the autologous resting T cell compartment. Applying this method to define putatively peanut protein-specific repertoires in 27 peanut-allergic individuals resulted in a library of 7345 unique CDR3β amino acid sequences that had similar characteristics to other validated antigen-specific repertoires in terms of homology and diversity. In-depth analysis of these CDR3βs revealed 36 public sequences that demonstrated high levels of convergent recombination. In a network analysis, the public CDR3βs were shown to be core sequences with more edges than their private counterparts. This method has the potential to be applied to a wide range of T cell-mediated disorders and to yield new biomarkers and biological insights. |
| first_indexed | 2024-09-23T14:47:55Z |
| format | Article |
| id | mit-1721.1/135626 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:47:55Z |
| publishDate | 2021 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | mit-1721.1/1356262023-10-06T19:50:29Z Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals Smith, Neal P Ruiter, Bert Virkud, Yamini V Tu, Ang A Monian, Brinda Moon, James J Love, J Christopher Shreffler, Wayne G Massachusetts Institute of Technology. Department of Physics Recent advances in high-throughput T cell receptor (TCR) sequencing have allowed for new insights into the human TCR repertoire. However, methods for capturing antigen-specific repertoires remain an area of development. Here, we describe a potentially novel approach that utilizes both a biological and statistical enrichment to define putatively antigen-specific complementarity-determining region 3 (CDR3) repertoires in unselected individuals. The biological enrichment entailed FACS of in vitro antigen-activated memory CD4+ T cells, followed by TCRβ sequencing. The resulting TCRβ sequences were then filtered by selecting those that are statistically enriched when compared with their frequency in the autologous resting T cell compartment. Applying this method to define putatively peanut protein-specific repertoires in 27 peanut-allergic individuals resulted in a library of 7345 unique CDR3β amino acid sequences that had similar characteristics to other validated antigen-specific repertoires in terms of homology and diversity. In-depth analysis of these CDR3βs revealed 36 public sequences that demonstrated high levels of convergent recombination. In a network analysis, the public CDR3βs were shown to be core sequences with more edges than their private counterparts. This method has the potential to be applied to a wide range of T cell-mediated disorders and to yield new biomarkers and biological insights. 2021-10-27T20:24:20Z 2021-10-27T20:24:20Z 2021 2021-07-12T12:37:55Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135626 en 10.1172/jci.insight.140028 JCI Insight Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Society for Clinical Investigation American Society for Clinical Investigation |
| spellingShingle | Smith, Neal P Ruiter, Bert Virkud, Yamini V Tu, Ang A Monian, Brinda Moon, James J Love, J Christopher Shreffler, Wayne G Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals |
| title | Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals |
| title_full | Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals |
| title_fullStr | Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals |
| title_full_unstemmed | Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals |
| title_short | Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals |
| title_sort | identification of antigen specific tcr sequences based on biological and statistical enrichment in unselected individuals |
| url | https://hdl.handle.net/1721.1/135626 |
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