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Of mice and humans: how good are HLA transgenic mice as a model of human immune responses?
Maya F Kotturi , Erika Assarsson , Bjoern Peters , Howard Grey , Carla Oseroff , Valerie Pasquetto and Alessandro Sette
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA
Previous studies have defined vaccinia virus (VACV)-derived T cell
epitopes in VACV-infected human leukocyte antigen-A*0201 (HLA-A2.1)
transgenic (Tg) mice and A2.1-positive human Dryvax vaccinees. A total
of 14 epitopes were detected in humans and 16 epitopes in A2.1 Tg mice;
however, only two epitopes were independently reported in both systems.
This limited overlap raised questions about the suitability of using
HLA Tg mice as a model system to map human T cell responses to a
complex viral pathogen. The present study was designed to investigate
this issue in more detail.
Re-screening the panel of 28 A2.1-restricted epitopes in additional
human vaccinees and in A2.1 Tg mice revealed that out of the 28
identified epitopes, 13 were detectable in both systems, corresponding
to a 46% concordance rate. Interestingly, the magnitude of responses in
Tg mice against epitopes originally identified in humans is lower than
for epitopes originally detected in mice. Likewise, responses in humans
against epitopes originally detected in Tg mice are of lower magnitude.
These data suggest that differences in immunodominance patterns
might explain the incomplete response overlap, and that with
limitations; HLA Tg mice represent a relevant and suitable model system
to study immune responses against complex pathogens.