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.
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.
Pajot
Anthony
A
Unité d'Immunité Cellulaire Antivirale, INSERM U370, Institut Pasteur, Paris, France.
Pancré
Véronique
V
Fazilleau
Nicolas
N
Michel
Marie-Louise
ML
Angyalosi
Gerhild
G
Ojcius
David M
DM
Auriault
Claude
C
Lemonnier
François A
FA
Lone
Yu-Chun
YC
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
D016207:Cytokines; D006183:H-2 Antigens; D015798:HLA-DR1 Antigen; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens