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. |