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International Immunology Advance Access published online on July 12, 2004
International Immunology, doi:10.1093/intimm/dxh129
© 2004 by The Japanese Society for Immunology
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Received February 25, 2004
Accepted June 17, 2004

Article

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

Anthony Pajot 1, Véronique Pancré 2, Nicolas Fazilleau 3, Marie-Louise Michel 4, Gerhild Angyalosi 2, David M. Ojcius 5, Claude Auriault 2, François A. Lemonnier 1, Yu-Chun Lone 1*

1 Unité d'Immunité Cellulaire Antivirale, INSERM U370, Institut Pasteur, Paris, France
2 Laboratoire d'Immunopathologie Cellulaire des maladies infectieuses, CNRS l'UMR 8527 de l'Institut de Biologie, Lille, France
3 Unité Biologie Moleculaire du Gène, INSERM U370, Institut Pasteur, Paris, France
4 Unité de carcinogenese hépatique et Virologie Moléculaire, INSERM U370, Institut Pasteur, Paris, France
5 School of Natural Sciences, University of California, Merced, CA 95344, USA

* To whom correspondence should be addressed. E-mail: lone{at}pasteur.fr.


  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+/+/IA{beta}0/0) 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+/+/IA{beta}+/+). More importantly, a strong antigen-specific HLA-DR1-restricted response was observed in nearly all HLA-DR1+/+/IA{beta}0/0 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+/+/IA{beta}+/+ mice. Conversely, strong HBs- or HBc-specific H-2-restricted T cell responses were detected in HLA-DR1+/+/IA{beta}+/+ mice but not in HLA-DR1+/+/IA{beta}0/0 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+/+/IA{beta}0/0 mice represent a better model for identifying and characterizing HLA-DR1-restricted epitopes relevant for human disease.

Keywords: antigen; major histocompatibility complex; transgenic mice; vaccine.
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