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HLA Class I-Restricted Viral T Cell Epitopes Identification and Characterization of New Deficient for H2 Class I Expression Facilitate Human MHC Class I Transgenic Mice

Although mice transgenic (Tg) for human MHC (HLA) class I alleles could provide an important model for characterizing HLA-restricted viral and tumor Ag CTL epitopes, the extent to which Tg mouse T cells become HLA restricted in the presence of endogenous H2 class I and recognize the same peptides as in HLA allele-matched humans is not clear. We previously described Tg mice carrying the HLA-B27, HLA-B7, or HLA-A2 alleles expressed as fully native (HLA nat ) (with human (cid:1) 2 -microglobulin) and as hybrid human/mouse (HLA hyb ) molecules on the H2 b background. To eliminate the inﬂuence of H2 b class I, each HLA Tg strain was bred with a H2-K b /H2-D b -double knockout (DKO) strain to generate mice in which the only classical class I expression was the human molecule. Expression of each HLA hyb molecule and HLA-B27 nat /human (cid:1) 2 -microglobulin led to peripheral CD8 (cid:2) T cell levels comparable with that for mice expressing a single H2-K b or H2-D b gene. Inﬂuenza A infection of Tg HLA-B27 hyb / DKO generated a strong CD8 (cid:2) T cell response directed at the same peptide (ﬂu nucleoprotein NP383–391) recognized by CTLs from ﬂu-infected B27 (cid:2) humans. As HLA-B7/ﬂu epitopes were not known from human studies, we used ﬂu-infected Tg HLA-B7 hyb /DKO mice to examine the CTL response to candidate peptides identiﬁed based on the B7 binding motif. We have identiﬁed