Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19.
The evolution of peptide-specific CD4(+) T-cell responses to acute viral infections of humans is poorly understood. We analyzed the response to parvovirus B19 (B19), a ubiquitous and clinically significant pathogen with a compact and conserved genome. The magnitude and breadth of the CD4(+) T-cell r...
| Autori principali: | , , , , , |
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| Natura: | Journal article |
| Lingua: | English |
| Pubblicazione: |
2006
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| _version_ | 1826268445918887936 |
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| author | Kasprowicz, V Isa, A Tolfvenstam, T Jeffery, K Bowness, P Klenerman, P |
| author_facet | Kasprowicz, V Isa, A Tolfvenstam, T Jeffery, K Bowness, P Klenerman, P |
| author_sort | Kasprowicz, V |
| collection | OXFORD |
| description | The evolution of peptide-specific CD4(+) T-cell responses to acute viral infections of humans is poorly understood. We analyzed the response to parvovirus B19 (B19), a ubiquitous and clinically significant pathogen with a compact and conserved genome. The magnitude and breadth of the CD4(+) T-cell response to the two B19 capsid proteins were investigated using a set of overlapping peptides and gamma interferon-specific enzyme-linked immunospot assays of peripheral blood mononuclear cells (PBMCs) from a cohort of acutely infected individuals who presented with acute arthropathy. These were compared to those for a cohort of B19-specific immunoglobulin M-negative (IgM(-)), IgG(+) remotely infected individuals. Both cohorts of individuals were found to make broad CD4(+) responses. However, while the responses following acute infection were detectable ex vivo, responses in remotely infected individuals were only detected after culture. One epitope (LASEESAFYVLEHSSFQLLG) was consistently targeted by both acutely (10/12) and remotely (6/7) infected individuals. This epitope was DRB1*1501 restricted, and a major histocompatibility complex peptide tetramer stained PBMCs from acutely infected individuals in the range of 0.003 to 0.042% of CD4(+) T cells. Tetramer-positive populations were initially CD62L(lo); unlike the case for B19-specific CD8(+) T-cell responses, however, CD62L was reexpressed at later times, as responses remained stable or declined slowly. This first identification of B19 CD4(+) T-cell epitopes, including a key immunodominant peptide, provides the tools to investigate the breadth, frequency, and functions of cellular responses to this virus in a range of specific clinical settings and gives an important reference point for analysis of peptide-specific CD4(+) T cells during acute and persistent virus infections of humans. |
| first_indexed | 2024-03-06T21:09:46Z |
| format | Journal article |
| id | oxford-uuid:3dbe12e5-15ef-4458-9871-d3e86f51bc95 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:09:46Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:3dbe12e5-15ef-4458-9871-d3e86f51bc952022-03-26T14:21:12ZTracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3dbe12e5-15ef-4458-9871-d3e86f51bc95EnglishSymplectic Elements at Oxford2006Kasprowicz, VIsa, ATolfvenstam, TJeffery, KBowness, PKlenerman, PThe evolution of peptide-specific CD4(+) T-cell responses to acute viral infections of humans is poorly understood. We analyzed the response to parvovirus B19 (B19), a ubiquitous and clinically significant pathogen with a compact and conserved genome. The magnitude and breadth of the CD4(+) T-cell response to the two B19 capsid proteins were investigated using a set of overlapping peptides and gamma interferon-specific enzyme-linked immunospot assays of peripheral blood mononuclear cells (PBMCs) from a cohort of acutely infected individuals who presented with acute arthropathy. These were compared to those for a cohort of B19-specific immunoglobulin M-negative (IgM(-)), IgG(+) remotely infected individuals. Both cohorts of individuals were found to make broad CD4(+) responses. However, while the responses following acute infection were detectable ex vivo, responses in remotely infected individuals were only detected after culture. One epitope (LASEESAFYVLEHSSFQLLG) was consistently targeted by both acutely (10/12) and remotely (6/7) infected individuals. This epitope was DRB1*1501 restricted, and a major histocompatibility complex peptide tetramer stained PBMCs from acutely infected individuals in the range of 0.003 to 0.042% of CD4(+) T cells. Tetramer-positive populations were initially CD62L(lo); unlike the case for B19-specific CD8(+) T-cell responses, however, CD62L was reexpressed at later times, as responses remained stable or declined slowly. This first identification of B19 CD4(+) T-cell epitopes, including a key immunodominant peptide, provides the tools to investigate the breadth, frequency, and functions of cellular responses to this virus in a range of specific clinical settings and gives an important reference point for analysis of peptide-specific CD4(+) T cells during acute and persistent virus infections of humans. |
| spellingShingle | Kasprowicz, V Isa, A Tolfvenstam, T Jeffery, K Bowness, P Klenerman, P Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19. |
| title | Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19. |
| title_full | Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19. |
| title_fullStr | Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19. |
| title_full_unstemmed | Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19. |
| title_short | Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19. |
| title_sort | tracking of peptide specific cd4 t cell responses after an acute resolving viral infection a study of parvovirus b19 |
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