Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals
Name
140028.2-20210623120355-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Description
Published version
Size
1.42 MB
Format
Adobe PDF
Checksum (MD5)
00607c43e7db71299115b5b558688420
Author(s)
Smith, Neal P
Ruiter, Bert
Virkud, Yamini V
Tu, Ang A
Monian, Brinda
Moon, James J
Love, J Christopher
Shreffler, Wayne G
Date Issued
2021
Journal
JCI Insight
Publisher
American Society for Clinical Investigation
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1172/jci.insight.140028
