title: Comparison of HLA-DR1-restricted T cell response induced in HLA-DR1 transgenic mice deficient for murine MHC class II and HLA-DR1 transgenic mice expressing endogenous murine MHC class II molecules.
abstract: Transgenic mice expressing human HLA class II molecules provide a useful model for identifying HLA-restricted CD4+ epitopes. However, the influence of endogenous murine H-2-restricted T cell responses on HLA-restricted responses is not known. In the present study, we show that HLA-DR1 transgenic mice deficient for H-2 class II expression (HLA-DR1+/+/IAbeta0/0) exhibit an equivalent expression level of the transgene HLA-DR1 and a similar diversity in the TCR repertoire, but a slightly different number of CD4+ peripheral T cells, when compared to HLA-DR1 transgenic mice in which H-2 class II molecules were retained (HLA-DR1+/+/IAbeta+/+). More importantly, a strong antigen-specific HLA-DR1-restricted response was observed in nearly all HLA-DR1+/+/IAbeta0/0 mice immunized with HBV envelope protein (HBs) or capsid protein (HBc), whereas weak HBs- or HBc-specific HLA-DR1-restricted responses were detected in half of the immunized HLA-DR1+/+/IAbeta+/+ mice. Conversely, strong HBs- or HBc-specific H-2-restricted T cell responses were detected in HLA-DR1+/+/IAbeta+/+ mice but not in HLA-DR1+/+/IAbeta0/0 mice. Our results indicate that the coexpression of endogenous H-2 class II molecules reduces the intensity of HLA-DR1-restricted antigen-specific responses in transgenic mice, by favoring murine over human MHC recognition and education. Thus, HLA-DR1+/+/IAbeta0/0 mice represent a better model for identifying and characterizing HLA-DR1-restricted epitopes relevant for human disease.
authors.affiliation: Unité d'Immunité Cellulaire Antivirale, INSERM U370, Institut Pasteur, Paris, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Pajot
authors.forename: Véronique
authors.initials: V
authors.lastname: Pancré
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fazilleau
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Michel
authors.forename: Gerhild
authors.initials: G
authors.lastname: Angyalosi
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.forename: Claude
authors.initials: C
authors.lastname: Auriault
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lone
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D018604:Epitope Mapping; D019674:Genes, T-Cell Receptor beta; D006183:H-2 Antigens / Q000502:physiology*; D015798:HLA-DR1 Antigen / Q000502:physiology*; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016207:Cytokines; D006183:H-2 Antigens; D015798:HLA-DR1 Antigen; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens