The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region.
Large cellular antigens comprise a variety of different epitopes leading to a T cell response of extreme diversity. Therefore, tracking such a response by next generation sequencing of the T cell receptor (TCR) in order to identify common TCR properties among the expanding T cells represents an enor...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0273264 |
| _version_ | 1811262285673398272 |
|---|---|
| author | Martin Meinhardt Cornelia Tune Lisa-Kristin Schierloh Andrea Schampel René Pagel Jürgen Westermann |
| author_facet | Martin Meinhardt Cornelia Tune Lisa-Kristin Schierloh Andrea Schampel René Pagel Jürgen Westermann |
| author_sort | Martin Meinhardt |
| collection | DOAJ |
| description | Large cellular antigens comprise a variety of different epitopes leading to a T cell response of extreme diversity. Therefore, tracking such a response by next generation sequencing of the T cell receptor (TCR) in order to identify common TCR properties among the expanding T cells represents an enormous challenge. In the present study we adapted a set of established indices to elucidate alterations in the TCR repertoire regarding sequence similarities between TCRs including VJ segment usage and diversity of nucleotide coding of a single TCR. We combined the usage of these indices with a new systematic splitting strategy regarding the copy number of the extracted clones to divide the repertoire into multiple fractions for separate analysis. We implemented this new analytic approach using the splenic TCR repertoire following immunization with sheep red blood cells (SRBC) in mice. As expected, early after immunization presumably antigen-specific clones accumulated in high copy number fractions, but at later time points similar accumulation of specific clones occurred within the repertoire fractions of lowest copy number. For both repertoire regions immunized animals could reliably be distinguished from control in a classification approach, demonstrating the robustness of the two effects at the individual level. The direction in which the indices shifted after immunization revealed that for both the early and the late effect alterations in repertoire parameters were caused by antigen-specific private clones displacing non-specific public clones. Taken together, tracking antigen-specific clones by their displacement of average TCR repertoire characteristics in standardized repertoire fractions ensures that our analytical approach is fairly independent from the antigen in question and thus allows the in-depth characterization of a variety of immune responses. |
| first_indexed | 2024-04-12T19:22:34Z |
| format | Article |
| id | doaj.art-2bab8932c4264ccf87e822f1642f5f5f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T19:22:34Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2bab8932c4264ccf87e822f1642f5f5f2022-12-22T03:19:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01178e027326410.1371/journal.pone.0273264The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region.Martin MeinhardtCornelia TuneLisa-Kristin SchierlohAndrea SchampelRené PagelJürgen WestermannLarge cellular antigens comprise a variety of different epitopes leading to a T cell response of extreme diversity. Therefore, tracking such a response by next generation sequencing of the T cell receptor (TCR) in order to identify common TCR properties among the expanding T cells represents an enormous challenge. In the present study we adapted a set of established indices to elucidate alterations in the TCR repertoire regarding sequence similarities between TCRs including VJ segment usage and diversity of nucleotide coding of a single TCR. We combined the usage of these indices with a new systematic splitting strategy regarding the copy number of the extracted clones to divide the repertoire into multiple fractions for separate analysis. We implemented this new analytic approach using the splenic TCR repertoire following immunization with sheep red blood cells (SRBC) in mice. As expected, early after immunization presumably antigen-specific clones accumulated in high copy number fractions, but at later time points similar accumulation of specific clones occurred within the repertoire fractions of lowest copy number. For both repertoire regions immunized animals could reliably be distinguished from control in a classification approach, demonstrating the robustness of the two effects at the individual level. The direction in which the indices shifted after immunization revealed that for both the early and the late effect alterations in repertoire parameters were caused by antigen-specific private clones displacing non-specific public clones. Taken together, tracking antigen-specific clones by their displacement of average TCR repertoire characteristics in standardized repertoire fractions ensures that our analytical approach is fairly independent from the antigen in question and thus allows the in-depth characterization of a variety of immune responses.https://doi.org/10.1371/journal.pone.0273264 |
| spellingShingle | Martin Meinhardt Cornelia Tune Lisa-Kristin Schierloh Andrea Schampel René Pagel Jürgen Westermann The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region. PLoS ONE |
| title | The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region. |
| title_full | The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region. |
| title_fullStr | The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region. |
| title_full_unstemmed | The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region. |
| title_short | The splenic T cell receptor repertoire during an immune response against a complex antigen: Expanding private clones accumulate in the high and low copy number region. |
| title_sort | splenic t cell receptor repertoire during an immune response against a complex antigen expanding private clones accumulate in the high and low copy number region |
| url | https://doi.org/10.1371/journal.pone.0273264 |
| work_keys_str_mv | AT martinmeinhardt thesplenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT corneliatune thesplenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT lisakristinschierloh thesplenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT andreaschampel thesplenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT renepagel thesplenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT jurgenwestermann thesplenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT martinmeinhardt splenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT corneliatune splenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT lisakristinschierloh splenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT andreaschampel splenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT renepagel splenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion AT jurgenwestermann splenictcellreceptorrepertoireduringanimmuneresponseagainstacomplexantigenexpandingprivateclonesaccumulateinthehighandlowcopynumberregion |