Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype.

We have applied a sensitive global analysis of TCR heterogeneity to compare clonal dynamics of CD4(+) and CD8(+) T cells in acute infectious mononucleosis. Using this approach, we are able to identify a broad representation of the total virus-specific population without the bias of in vitro culture...

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Main Authors: Maini, M, Gudgeon, N, Wedderburn, L, Rickinson, AB, Beverley, P
Format: Journal article
Language:English
Published: 2000
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author Maini, M
Gudgeon, N
Wedderburn, L
Rickinson, AB
Beverley, P
author_facet Maini, M
Gudgeon, N
Wedderburn, L
Rickinson, AB
Beverley, P
author_sort Maini, M
collection OXFORD
description We have applied a sensitive global analysis of TCR heterogeneity to compare clonal dynamics of CD4(+) and CD8(+) T cells in acute infectious mononucleosis. Using this approach, we are able to identify a broad representation of the total virus-specific population without the bias of in vitro culture and then to track their phenotype and fate by their unique molecular footprint. We demonstrate a large number of Ag-driven clones using different TCRs in the acute phase, all CD8(+). The diverse large clones generated in the CD8 subset in response to this virus contrast with the complete lack of detectable clonal expansion in the CD4 compartment. Many of the same clones remain detectable in directly ex vivo CD8(+) T cells for at least a year after resolution of infectious mononucleosis, although the clone size is reduced. Thus, memory CD8 cells following EBV infection persist at relatively high circulating frequency and represent a subset of the large range of clonotypes comprising the acute effectors. Separation of samples into CD45RA (naive) and CD45RO (memory) fractions shows the accumulation of identical CDR3 region defined clonotypes in both CD45RO and CD45RA fractions and sequencing confirms that dominant long-lived monoclonal expansions can reside in the CD45RA pool.
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spelling oxford-uuid:90c2aaf7-0eb6-4ce9-bde9-a00aa1e165ff2022-03-26T23:13:55ZClonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:90c2aaf7-0eb6-4ce9-bde9-a00aa1e165ffEnglishSymplectic Elements at Oxford2000Maini, MGudgeon, NWedderburn, LRickinson, ABBeverley, PWe have applied a sensitive global analysis of TCR heterogeneity to compare clonal dynamics of CD4(+) and CD8(+) T cells in acute infectious mononucleosis. Using this approach, we are able to identify a broad representation of the total virus-specific population without the bias of in vitro culture and then to track their phenotype and fate by their unique molecular footprint. We demonstrate a large number of Ag-driven clones using different TCRs in the acute phase, all CD8(+). The diverse large clones generated in the CD8 subset in response to this virus contrast with the complete lack of detectable clonal expansion in the CD4 compartment. Many of the same clones remain detectable in directly ex vivo CD8(+) T cells for at least a year after resolution of infectious mononucleosis, although the clone size is reduced. Thus, memory CD8 cells following EBV infection persist at relatively high circulating frequency and represent a subset of the large range of clonotypes comprising the acute effectors. Separation of samples into CD45RA (naive) and CD45RO (memory) fractions shows the accumulation of identical CDR3 region defined clonotypes in both CD45RO and CD45RA fractions and sequencing confirms that dominant long-lived monoclonal expansions can reside in the CD45RA pool.
spellingShingle Maini, M
Gudgeon, N
Wedderburn, L
Rickinson, AB
Beverley, P
Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype.
title Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype.
title_full Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype.
title_fullStr Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype.
title_full_unstemmed Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype.
title_short Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype.
title_sort clonal expansions in acute ebv infection are detectable in the cd8 and not the cd4 subset and persist with a variable cd45 phenotype
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AT gudgeonn clonalexpansionsinacuteebvinfectionaredetectableinthecd8andnotthecd4subsetandpersistwithavariablecd45phenotype
AT wedderburnl clonalexpansionsinacuteebvinfectionaredetectableinthecd8andnotthecd4subsetandpersistwithavariablecd45phenotype
AT rickinsonab clonalexpansionsinacuteebvinfectionaredetectableinthecd8andnotthecd4subsetandpersistwithavariablecd45phenotype
AT beverleyp clonalexpansionsinacuteebvinfectionaredetectableinthecd8andnotthecd4subsetandpersistwithavariablecd45phenotype