Phenotypical and functional characterization of the CD8(+) T cell repertoire of HLA-A2.1 transgenic, H-2K(bo)D(bo) double knockout mice

Homozygous HLA-A2.1 transgenic N-2K(bo)D(bo) double knockout (KO) mice were created. Their potential to develop HLA-A2.1-restricted cytolytic response s was compared with that of their classical transgenic counterparts, which still express H-2K(b), Db molecules, On cell surfaces, both strains express similar amounts of chimeric (alpha 1 alpha 2 domains of human, alpha 3 cyt oplasmic domains of mouse) HLA-A2.1 molecules in noncovalent association wi th mouse beta(2),-microglobulin, Compared with mice that are totally depriv ed of histocompatibility class Ia molecules (H-2K(bo)D(bo) double KO), the expression of HLA-A2.1 in transgenic/double KO mice resulted in sizeable in crease in the periphery of CD8(+) T cells with a normally diversified TCR r epertoire. A biased education in favor of HLA-A2.1, ascribable to the absen ce of H-2 class Ia molecules, was evidenced in these transgenic/double KO m ice by their improved capacity to mount HLA-restricted cytolytic responses, regardless of whether they were virally infected or injected with syntheti c epitopic peptide. HLA class I transgenic, H-2 class Ia KO mice should rep resent useful animal models for the preclinical evaluation of vaccine formu lations aiming at the induction of HLA class I-restricted CTL responses.