International Immunology, Vol. 14, No. 8, pp. 925-934,
August 2002
© 2002 Japanese Society for Immunology
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
1 Généthon III, CNRS URA 1923, 1 bis rue de l’Internationale, BP 60, 91002 Evry Cedex, France 2 Unité d‘Immunité Cellulaire Antivirale, Département SIDA-Rétrovirus, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France 3 Hôpital Robert-Debré, 48 bd Serurier, 75019 Paris, France 4 Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France
Correspondence to: H. Firat, PCS/ICPP/Pharmacogenomics, WKL-136.182 Novartis Pharma AG, Werk Klybeck, Postfach CH-Basel, Switzerland. E-mail: huesevin.firat{at}pharma.novartis.com
Transmitting editor: C. Martinez-A
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/Kb 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 ß 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/Kb 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.
Keywords: cytotoxic T lymphocyte, HLA-A2.1, MHC, transgenic/knockout
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