Comparative analysis of the CD8(+) T cell repertoires of H-2 class I wild-type/HLA-A2.1 and H-2 class I knockout/HLA-A2.1 transgenic mice.
HHD transgenic mice which express HLA-A2.1 monochain molecules in a H-2 class I(-) context have an improved capacity to develop HLA-A2.1-restricted cytotoxic T lymphocyte (CTL) responses as compared with classical A2.1/K(b) transgenic mice, which express heterodimeric HLA-A2.1 molecules in a H-2 class I wild-type context. A detailed TCR analysis of HLA-A2.1-restricted CD8(+) T cells educated and mobilized in both strains of mice was undertaken. Focusing on TCR beta chains, comparative PCR analysis of naive and immune CD8(+) T cell repertoires were performed. In spite of lower cell surface expression of HLA class I molecules and lower overall number of CD8(+) T cells, HHD mice educate a qualitatively normally diversified CD8(+) T cell repertoire and mobilize a larger variety of CD8(+) T cells in response to HLA-A2.1-restricted antigens compared with A2.1/K(b) mice. These observations provide the molecular bases accounting for the fact that HHD mice represent the most versatile animal model currently available for preclinical studies of HLA-A2.1-restricted CTL responses.
Firat
Hüseyin
H
Généthon III, CNRS URA 1923, 1 bis rue de l'Internationale, BP 60, 91002 Evry Cedex, France. huesevin.firat@pharma.novartis.com
Cochet
Madeleine
M
Rohrlich
Pierre-Simon
PS
Garcia-Pons
Francisco
F
Darche
Sylvie
S
Danos
Olivier
O
Lemonnier
François A
FA
Langlade-Demoyen
Pierre
P
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D005805:Genes, MHC Class I; D019674:Genes, T-Cell Receptor beta; D006183:H-2 Antigens / Q000235:genetics*; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D022801:Complementarity Determining Regions; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D058951:gp100 Melanoma Antigen; D004247:DNA