A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex.
In this study, we have compared the effector functions and fate of a number of human CTL clones in vitro or ex vivo following contact with variant peptides presented either on the cell surface or in a soluble multimeric format. In the presence of CD8 coreceptor binding, there is a good correlation b...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2001
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| _version_ | 1826267150101250048 |
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| author | Xu, X Purbhoo, M Chen, N Mongkolsapaya, J Cox, J Meier, U Tafuro, S Dunbar, P Sewell, A Hourigan, C Appay, V Cerundolo, V Burrows, SR Mcmichael, A Screaton, G |
| author_facet | Xu, X Purbhoo, M Chen, N Mongkolsapaya, J Cox, J Meier, U Tafuro, S Dunbar, P Sewell, A Hourigan, C Appay, V Cerundolo, V Burrows, SR Mcmichael, A Screaton, G |
| author_sort | Xu, X |
| collection | OXFORD |
| description | In this study, we have compared the effector functions and fate of a number of human CTL clones in vitro or ex vivo following contact with variant peptides presented either on the cell surface or in a soluble multimeric format. In the presence of CD8 coreceptor binding, there is a good correlation between TCR signaling, killing of the targets, and FasL-mediated CTL apoptosis. Blocking CD8 binding using alpha3 domain mutants of MHC class I results in much reduced signaling and reduced killing of the targets. Surprisingly, however, FasL expression is induced to a similar degree on these CTLs, and apoptosis of CTL is unaffected. The ability to divorce these events may allow the deletion of antigen-specific and pathological CTL populations without the deleterious effects induced by full CTL activation. |
| first_indexed | 2024-03-06T20:49:47Z |
| format | Journal article |
| id | oxford-uuid:372c8811-6340-4d23-af46-333056053374 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:49:47Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:372c8811-6340-4d23-af46-3330560533742022-03-26T13:42:29ZA novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:372c8811-6340-4d23-af46-333056053374EnglishSymplectic Elements at Oxford2001Xu, XPurbhoo, MChen, NMongkolsapaya, JCox, JMeier, UTafuro, SDunbar, PSewell, AHourigan, CAppay, VCerundolo, VBurrows, SRMcmichael, AScreaton, GIn this study, we have compared the effector functions and fate of a number of human CTL clones in vitro or ex vivo following contact with variant peptides presented either on the cell surface or in a soluble multimeric format. In the presence of CD8 coreceptor binding, there is a good correlation between TCR signaling, killing of the targets, and FasL-mediated CTL apoptosis. Blocking CD8 binding using alpha3 domain mutants of MHC class I results in much reduced signaling and reduced killing of the targets. Surprisingly, however, FasL expression is induced to a similar degree on these CTLs, and apoptosis of CTL is unaffected. The ability to divorce these events may allow the deletion of antigen-specific and pathological CTL populations without the deleterious effects induced by full CTL activation. |
| spellingShingle | Xu, X Purbhoo, M Chen, N Mongkolsapaya, J Cox, J Meier, U Tafuro, S Dunbar, P Sewell, A Hourigan, C Appay, V Cerundolo, V Burrows, SR Mcmichael, A Screaton, G A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex. |
| title | A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex. |
| title_full | A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex. |
| title_fullStr | A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex. |
| title_full_unstemmed | A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex. |
| title_short | A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex. |
| title_sort | novel approach to antigen specific deletion of ctl with minimal cellular activation using alpha3 domain mutants of mhc class i peptide complex |
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