Phenotypical and functional characterization of the CD8+ T cell repertoire of HLA-A2.1 transgenic, H-2KbnullDbnull double knockout mice.
Homozygous HLA-A2.1 transgenic H-2KbnullDbnull 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 (alpha 1 alpha 2 domains of human, alpha 3 cytoplasmic domains of mouse) HLA-A2.1 molecules in noncovalent association with mouse beta 2-microglobulin. Compared with mice that are totally deprived of histocompatibility class Ia molecules (H-2KbnullDbnull 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.
Ureta-Vidal
A
A
Unité d'Immunité Cellulaire Antivirale, Département SIDA-Rétrovirus, Institut Pasteur, Paris, France.
Firat
H
H
Pérarnau
B
B
Lemonnier
F A
FA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D006183:H-2 Antigens / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000494:pharmacology; D015789:HLA-A2 Antigen / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D054303:HIV Reverse Transcriptase