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Epitope-dependent s...
Epitope-dependent selection of highly restricted or diverse T cell receptor repertoires in response to persistent infection by Epstein-Barr virus
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deCamposLima, PO (författare)
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- Levitsky, V (författare)
- Karolinska Institutet
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- Imreh, MP (författare)
- Karolinska Institutet
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Gavioli, R (författare)
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- Masucci, MG (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 1997-07-07
- 1997
- Engelska.
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 186:1, s. 83-89
- Relaterad länk:
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http://jem.rupress.o...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The T cell receptor (TCR) repertoires of cytotoxic responses to the immunodominant and subdominant HLA A11–restricted epitopes in the Epstein-Barr virus (EBV) nuclear antigen-4 were investigated in four healthy virus carriers. The response to the subdominant epitope (EBNA4 399-408, designated AVF) was highly restricted with conserved Vβ usage and identical length and amino acid motifs in the third complementarity-determining regions (CDR3), while a broad repertoire using different combinations of TCR-α/β V and J segments and CDR3 regions was selected by the immunodominant epitope (EBNA4 416-424, designated IVT). Distinct patterns of interaction with the A11–peptide complex were revealed for each AVF- or IVT-specific TCR clonotype by alanine scanning mutagenesis analysis. Blocking of cytotoxic function by antibodies specific for the CD8 coreceptor indicated that, while AVF-specific TCRs are of high affinity, the oligoclonal response to the IVT epitope includes both low- and high-affinity TCRs. Thus, comparison of the memory response to two epitopes derived from the same viral antigen and presented through the same MHC class I allele suggests that immunodominance may correlate with the capacity to maintain a broad TCR repertoire.
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