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Pattern of HLA allele co-expression influences immunodominance of anti-viral CTL responses

Posted on:2007-07-09Degree:M.ScType:Thesis
University:University of Toronto (Canada)Candidate:Akram, AliFull Text:PDF
GTID:2444390005967480Subject:Health Sciences
Abstract/Summary:
In order to assess whether co-expression of multiple, as opposed to expression of single, MHC class I alleles influences the pattern of anti-flu CTL epitope recognition and immunodominance (ImDc), doubly HLA transgenic (Tg) mice were established on a H2-K-/-/D-/- background. In flu-infected, doubly Tg A2/B7 or A2/B27 mice, IFN-gamma ELISpot assays with A2/M1.58-66 and B7/NP418-426 or B27/NP383-391 flu epitopes showed strong recognition of both peptides for both alleles. In contrast, in flu-infected doubly Tg B7/B27 mice, a reduced level of B27/NP383-restricted CTL response was detected while there was virtually no change in the response level of B7/NP418-restricted CTL. These results demonstrate a form of ImDe. Subsequent studies suggested that co-expression of HLA-B7 with HLA-B27 may lead to a partial deletion of Vbeta8.1+ B27/NP383-restricted CD8+ T cells in these doubly Tg B7/B27 mice.
Keywords/Search Tags:CTL, Co-expression, Doubly tg, Mice
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