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Unité d’Immunité Cellulaire Antivirale, Département SIDA-Rétrovirus, Institut Pasteur, Paris, France
Homozygous HLA-A2.1 transgenic
H-2Kb°Db°
double knockout (KO) mice were created. Their potential to develop
HLA-A2.1-restricted cytolytic responses was compared with that of their
classical transgenic counterparts, which still express
H-2Kb, Db molecules. On cell surfaces, both
strains express similar amounts of chimeric (
12 domains of human,
3 cytoplasmic domains of mouse) HLA-A2.1 molecules in noncovalent
association with mouse ß2-microglobulin. Compared with
mice that are totally deprived of histocompatibility class Ia molecules
(H-2Kb°Db°
double KO), the expression of HLA-A2.1 in transgenic/double KO mice
resulted in sizeable increase in the periphery of CD8+ T
cells with a normally diversified TCR repertoire. A biased education in
favor of HLA-A2.1, ascribable to the absence of H-2 class Ia molecules,
was evidenced in these transgenic/double KO mice by their improved
capacity to mount HLA-restricted cytolytic responses, regardless of
whether they were virally infected or injected with synthetic epitopic
peptide. HLA class I transgenic, H-2
class Ia KO mice should represent useful animal models for the
preclinical evaluation of vaccine formulations aiming at the induction
of HLA class I-restricted CTL responses.
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