Analysis of 'driver' and 'passenger' CD8+ T-cell responses against variable viruses.
Variable viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV), persist despite host immune responses directed against them. Numerous lines of evidence have suggested that antiviral CD8+ T-cell responses are key among these immune responses, but these vary widely in their a...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1826281296483057664 |
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| author | Zafiropoulos, A Barnes, E Piggott, C Klenerman, P |
| author_facet | Zafiropoulos, A Barnes, E Piggott, C Klenerman, P |
| author_sort | Zafiropoulos, A |
| collection | OXFORD |
| description | Variable viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV), persist despite host immune responses directed against them. Numerous lines of evidence have suggested that antiviral CD8+ T-cell responses are key among these immune responses, but these vary widely in their ability to contain virus. We propose that only a proportion of responses may exert significant antiviral pressure ('driver' responses), leading to control over viral replication (protection) and/or, ultimately, selection of escape mutants. Another set of responses may exert only weak pressure on the virus ('passenger' responses): these neither protect nor select. To examine this we have analysed (using established databases of HIV and HCV sequences and cytotoxic T-lymphocyte (CTL) epitopes, and published experimental datasets) two important features--predicted binding of the epitope to major histocompatibility complex molecule and observed variability of the epitope--that might distinguish such responses. We find that a high predicted binding estimate could only explain a limited set of 'driver' responses associated with protection or selection. There is statistical evidence that readily defined (and non-protective) CTL responses target regions associated with lower levels of viral variability. Taken together, this suggests that a large number of well-documented responses may represent 'passengers' and we propose a mechanism that might explain their presence. |
| first_indexed | 2024-03-07T00:26:40Z |
| format | Journal article |
| id | oxford-uuid:7e6014cc-965e-477b-b74d-2ffe464b4d8d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:26:40Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:7e6014cc-965e-477b-b74d-2ffe464b4d8d2022-03-26T21:09:42ZAnalysis of 'driver' and 'passenger' CD8+ T-cell responses against variable viruses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7e6014cc-965e-477b-b74d-2ffe464b4d8dEnglishSymplectic Elements at Oxford2004Zafiropoulos, ABarnes, EPiggott, CKlenerman, PVariable viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV), persist despite host immune responses directed against them. Numerous lines of evidence have suggested that antiviral CD8+ T-cell responses are key among these immune responses, but these vary widely in their ability to contain virus. We propose that only a proportion of responses may exert significant antiviral pressure ('driver' responses), leading to control over viral replication (protection) and/or, ultimately, selection of escape mutants. Another set of responses may exert only weak pressure on the virus ('passenger' responses): these neither protect nor select. To examine this we have analysed (using established databases of HIV and HCV sequences and cytotoxic T-lymphocyte (CTL) epitopes, and published experimental datasets) two important features--predicted binding of the epitope to major histocompatibility complex molecule and observed variability of the epitope--that might distinguish such responses. We find that a high predicted binding estimate could only explain a limited set of 'driver' responses associated with protection or selection. There is statistical evidence that readily defined (and non-protective) CTL responses target regions associated with lower levels of viral variability. Taken together, this suggests that a large number of well-documented responses may represent 'passengers' and we propose a mechanism that might explain their presence. |
| spellingShingle | Zafiropoulos, A Barnes, E Piggott, C Klenerman, P Analysis of 'driver' and 'passenger' CD8+ T-cell responses against variable viruses. |
| title | Analysis of 'driver' and 'passenger' CD8+ T-cell responses against variable viruses. |
| title_full | Analysis of 'driver' and 'passenger' CD8+ T-cell responses against variable viruses. |
| title_fullStr | Analysis of 'driver' and 'passenger' CD8+ T-cell responses against variable viruses. |
| title_full_unstemmed | Analysis of 'driver' and 'passenger' CD8+ T-cell responses against variable viruses. |
| title_short | Analysis of 'driver' and 'passenger' CD8+ T-cell responses against variable viruses. |
| title_sort | analysis of driver and passenger cd8 t cell responses against variable viruses |
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