Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes.
Some viruses, including human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in humans, and lymphocytic choriomeningitis virus (LCMV) in mice, are initially controlled by cytotoxic T lymphocytes (CTLs), but may subsequently escape through mutation of the relevant T-cell epitope. Some of th...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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1998
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| _version_ | 1797102101318336512 |
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| author | Klenerman, P Zinkernagel, R |
| author_facet | Klenerman, P Zinkernagel, R |
| author_sort | Klenerman, P |
| collection | OXFORD |
| description | Some viruses, including human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in humans, and lymphocytic choriomeningitis virus (LCMV) in mice, are initially controlled by cytotoxic T lymphocytes (CTLs), but may subsequently escape through mutation of the relevant T-cell epitope. Some of these mutations preserve the normal binding to major histocompatibility complex class I molecules, but present an altered surface to the T-cell antigen receptor. The exact role of these so-called altered peptide ligands in vivo is not clear. Here we report that mice primed with LCMV-WE strain respond to a subsequent infection by WE-derived CTL epitope variants with a CTL response directed against the initial epitope rather than against the new variant epitope. This phenomenon of 'original antigenic sin' was initially described in influenza and is an asymmetric pattern of protective antibody crossreactivity determined by exposure to previously existing strains, which may therefore extend to some CTL responses. Original antigenic sin by CTL leads to impaired clearance of variant viruses infecting the same individual and so may enhance the immune escape of mutant viruses evolving in an individual host. |
| first_indexed | 2024-03-07T06:01:07Z |
| format | Journal article |
| id | oxford-uuid:ec380dc7-1f4b-4615-855b-649493752a4b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:01:07Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:ec380dc7-1f4b-4615-855b-649493752a4b2022-03-27T11:15:48ZOriginal antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ec380dc7-1f4b-4615-855b-649493752a4bEnglishSymplectic Elements at Oxford1998Klenerman, PZinkernagel, RSome viruses, including human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in humans, and lymphocytic choriomeningitis virus (LCMV) in mice, are initially controlled by cytotoxic T lymphocytes (CTLs), but may subsequently escape through mutation of the relevant T-cell epitope. Some of these mutations preserve the normal binding to major histocompatibility complex class I molecules, but present an altered surface to the T-cell antigen receptor. The exact role of these so-called altered peptide ligands in vivo is not clear. Here we report that mice primed with LCMV-WE strain respond to a subsequent infection by WE-derived CTL epitope variants with a CTL response directed against the initial epitope rather than against the new variant epitope. This phenomenon of 'original antigenic sin' was initially described in influenza and is an asymmetric pattern of protective antibody crossreactivity determined by exposure to previously existing strains, which may therefore extend to some CTL responses. Original antigenic sin by CTL leads to impaired clearance of variant viruses infecting the same individual and so may enhance the immune escape of mutant viruses evolving in an individual host. |
| spellingShingle | Klenerman, P Zinkernagel, R Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. |
| title | Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. |
| title_full | Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. |
| title_fullStr | Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. |
| title_full_unstemmed | Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. |
| title_short | Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. |
| title_sort | original antigenic sin impairs cytotoxic t lymphocyte responses to viruses bearing variant epitopes |
| work_keys_str_mv | AT klenermanp originalantigenicsinimpairscytotoxictlymphocyteresponsestovirusesbearingvariantepitopes AT zinkernagelr originalantigenicsinimpairscytotoxictlymphocyteresponsestovirusesbearingvariantepitopes |