Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells.
A major breakthrough in cellular immunology has been the development of HLA class I tetramers to analyze CD8(+) T cell responses. However, in many situations, including persistent virus infection, specific T cell responses are rarely detected using this technology. This raises the question of whethe...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2004
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| _version_ | 1797070560415449088 |
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| author | Barnes, E Ward, S Kasprowicz, V Dusheiko, G Klenerman, P Lucas, M |
| author_facet | Barnes, E Ward, S Kasprowicz, V Dusheiko, G Klenerman, P Lucas, M |
| author_sort | Barnes, E |
| collection | OXFORD |
| description | A major breakthrough in cellular immunology has been the development of HLA class I tetramers to analyze CD8(+) T cell responses. However, in many situations, including persistent virus infection, specific T cell responses are rarely detected using this technology. This raises the question of whether such responses are 'deleted' (or 'exhausted') or present below the conventional detection limit for class I tetramer staining. In particular, persistent hepatitis C virus (HCV) infection is characterized by very weak or apparently absent specific CD8(+) T cell responses, even though they are readily detectable in acute disease. Therefore, we assessed the use of anti-PE-labeled magnetic beads to enrich tetramer-positive HCV-specific T cells and identify previously undetectable populations. Using the enrichment technique, HCV-specific T cells could be detected in the majority of infected individuals, whereas these responses were not detected using conventional tetramer staining (8/15 vs. 1/15; p=0.01). Magnetic enrichment could reliably detect very rare HCV-specific responses at frequencies of >0.0011% of CD8(+) T cells (approximately 1/million PBMC), and phenotypic analysis of these rare populations was possible. Therefore, this direct ex vivo technique revealed the persistence of very low frequencies of virus-specific CD8(+) T cells during chronic virus infection and is readily transferable to the study of other viral, self- or tumor-specific T cells. |
| first_indexed | 2024-03-06T22:40:37Z |
| format | Journal article |
| id | oxford-uuid:5b69655d-edcd-4b80-86a7-3a732d8487dc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:40:37Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:5b69655d-edcd-4b80-86a7-3a732d8487dc2022-03-26T17:21:56ZUltra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5b69655d-edcd-4b80-86a7-3a732d8487dcEnglishSymplectic Elements at Oxford2004Barnes, EWard, SKasprowicz, VDusheiko, GKlenerman, PLucas, MA major breakthrough in cellular immunology has been the development of HLA class I tetramers to analyze CD8(+) T cell responses. However, in many situations, including persistent virus infection, specific T cell responses are rarely detected using this technology. This raises the question of whether such responses are 'deleted' (or 'exhausted') or present below the conventional detection limit for class I tetramer staining. In particular, persistent hepatitis C virus (HCV) infection is characterized by very weak or apparently absent specific CD8(+) T cell responses, even though they are readily detectable in acute disease. Therefore, we assessed the use of anti-PE-labeled magnetic beads to enrich tetramer-positive HCV-specific T cells and identify previously undetectable populations. Using the enrichment technique, HCV-specific T cells could be detected in the majority of infected individuals, whereas these responses were not detected using conventional tetramer staining (8/15 vs. 1/15; p=0.01). Magnetic enrichment could reliably detect very rare HCV-specific responses at frequencies of >0.0011% of CD8(+) T cells (approximately 1/million PBMC), and phenotypic analysis of these rare populations was possible. Therefore, this direct ex vivo technique revealed the persistence of very low frequencies of virus-specific CD8(+) T cells during chronic virus infection and is readily transferable to the study of other viral, self- or tumor-specific T cells. |
| spellingShingle | Barnes, E Ward, S Kasprowicz, V Dusheiko, G Klenerman, P Lucas, M Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. |
| title | Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. |
| title_full | Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. |
| title_fullStr | Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. |
| title_full_unstemmed | Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. |
| title_short | Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. |
| title_sort | ultra sensitive class i tetramer analysis reveals previously undetectable populations of antiviral cd8 t cells |
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