Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses.
Assessment of clonal diversity of T cell responses against human CMV (HCMV), a major cause of morbidity in immunodepressed patients, provides important insights into the molecular basis of T cell immunodominance, and has also clinical implications for the immunomonitoring and immunotherapy of HCMV i...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2005
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| _version_ | 1797080419486662656 |
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| author | Trautmann, L Rimbert, M Echasserieau, K Saulquin, X Neveu, B Dechanet, J Cerundolo, V Bonneville, M |
| author_facet | Trautmann, L Rimbert, M Echasserieau, K Saulquin, X Neveu, B Dechanet, J Cerundolo, V Bonneville, M |
| author_sort | Trautmann, L |
| collection | OXFORD |
| description | Assessment of clonal diversity of T cell responses against human CMV (HCMV), a major cause of morbidity in immunodepressed patients, provides important insights into the molecular basis of T cell immunodominance, and has also clinical implications for the immunomonitoring and immunotherapy of HCMV infections. We performed an in-depth molecular and functional characterization of CD8 T cells directed against an immunodominant HLA-A2-restricted epitope derived from HCMV protein pp65 (NLV/A2) in steady state and pathological situations associated with HCMV reactivation. NLV/A2-specific T cells in healthy HCMV-seropositive donors showed limited clonal diversity and usage of a restricted set of TCR Vbeta regions. Although TCRbeta-chain junctional sequences were highly diverse, a large fraction of NLV/A2-specific T cells derived from distinct individuals showed several recurrent (so-called "public") TCR features associated in some cases with full conservation of the TCRalpha chain junctional region. A dramatic clonal focusing of NLV/A2-specific T cells was observed in situations of HCMV reactivation and/or chronic inflammation, which resulted in selection of a single clonotype displaying similar public TCR features in several patients. In most instances the NLV/A2-specific dominant clonotypes showed higher affinity for their Ag than subdominant ones, thus suggesting that TCR affinity/avidity is the primary driving force underlying repertoire focusing along chronic antigenic stimulation. |
| first_indexed | 2024-03-07T00:59:46Z |
| format | Journal article |
| id | oxford-uuid:89507bbc-a8b6-4e90-997c-c8c474df01e1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:59:46Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:89507bbc-a8b6-4e90-997c-c8c474df01e12022-03-26T22:23:40ZSelection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:89507bbc-a8b6-4e90-997c-c8c474df01e1EnglishSymplectic Elements at Oxford2005Trautmann, LRimbert, MEchasserieau, KSaulquin, XNeveu, BDechanet, JCerundolo, VBonneville, MAssessment of clonal diversity of T cell responses against human CMV (HCMV), a major cause of morbidity in immunodepressed patients, provides important insights into the molecular basis of T cell immunodominance, and has also clinical implications for the immunomonitoring and immunotherapy of HCMV infections. We performed an in-depth molecular and functional characterization of CD8 T cells directed against an immunodominant HLA-A2-restricted epitope derived from HCMV protein pp65 (NLV/A2) in steady state and pathological situations associated with HCMV reactivation. NLV/A2-specific T cells in healthy HCMV-seropositive donors showed limited clonal diversity and usage of a restricted set of TCR Vbeta regions. Although TCRbeta-chain junctional sequences were highly diverse, a large fraction of NLV/A2-specific T cells derived from distinct individuals showed several recurrent (so-called "public") TCR features associated in some cases with full conservation of the TCRalpha chain junctional region. A dramatic clonal focusing of NLV/A2-specific T cells was observed in situations of HCMV reactivation and/or chronic inflammation, which resulted in selection of a single clonotype displaying similar public TCR features in several patients. In most instances the NLV/A2-specific dominant clonotypes showed higher affinity for their Ag than subdominant ones, thus suggesting that TCR affinity/avidity is the primary driving force underlying repertoire focusing along chronic antigenic stimulation. |
| spellingShingle | Trautmann, L Rimbert, M Echasserieau, K Saulquin, X Neveu, B Dechanet, J Cerundolo, V Bonneville, M Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. |
| title | Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. |
| title_full | Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. |
| title_fullStr | Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. |
| title_full_unstemmed | Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. |
| title_short | Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. |
| title_sort | selection of t cell clones expressing high affinity public tcrs within human cytomegalovirus specific cd8 t cell responses |
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