Antiviral Cell Immunology

  HEADProf. LEMONNIER François /
  MEMBERSBAWA Olivia / BOUZIAT Romain / Dr HUETZ François / KRIDANE Hédia / Dr LAIKA Taghrid
Dr LONE Yu chun / RIOU Sylvain / Dr ROTH Claude / Dr SALMON Jerôme / Dr TOURDOT Sophie

  Annual Report

1. HLA transgenic H-2 KO strains of mice for vaccine research (R. Bouziat, YC. Lone and S. Tourdot)

The following strains, homozygous for all the listed characters, are available: HLA-A02.01, HLA-DR1 (or -DR3, or -DQ8) H-2 class I/class II KO ; HLA-DP4, human CD4, H-2 class II KO, mouse CD4 KO. These mice and 2 additional strains (HLA-A24, H-2 class I KO and HLA-A3.1, H-2 class I KO) have been used to identify new Hepatitis B and HIV-1-derived T cell epitopes and to compare their intrinsic immunogenicity. Structurally conserved epitopes of proven immunogenicity have been (HLA-A2, -B7) or will be (HLA-A24, -A3) inserted in polyepitope constructs that should be of interest for a large fraction of individuals in human populations.

Collaborators: M.-L. Michel, Département de Virologie; P. Charneau, Unité de Virologie Moléculaire et Vectorologie; A. Six, Unité d’Immunophysiopathologie.

2. Humanized animal model for type I diabetis (T. Laika).

This work is headed on a collaborative basis by Pr C. Boitard, INSERM U561, Paris. Five peptides from human and mouse preproinsulins have been identified that stimulate HLA-A2-restricted cytolytic responses in HLA-A2 transgenic mice. Four preproinsulin peptides have been shown to stimulate HLA-DQ8-restricted T cell proliferative responses.

HLA-A2, HLA-DQ8 H-2 class I class II KO mice are currently crossed with human preproinsulin transgenic, mouse preproinsulin 1 and 2 KO mice and the experimental conditions that could break tolerance to preproinsulin are explored.

3. T cell recognition of Hfe molecule (S. Tourdot and F. Lemonnier).

Hfe, a MHC class Ib molecule that has no antigen-presenting function (its peptide groove is narrow and empty) regulates iron metabolism. Nevertheless, Hfe stimulates directly cytolytic responses mediated by αβ TCR CD8+ T cells. We are exploring the physiological relevance of this interface between the immune system and iron metabolism and the possibility that Hfe could be, on its own, a histocompatibility molecule. Transgenic mice expressing an Hfe-specific TCR have been created to address these questions.

Collaborators: P. Rohrlich, R. Boucherma, INSERM U645, Besançon, France ; K.C. Garcia, Stanford, CA ; J. Kanellopoulos, UMR 8619, CNRS, Orsay, France.

4. Natural Killer (NK) cell differentiation (S. Riou and C. Roth).

This work has established that the terminal differentiation of NK cells (an essential cellular component of innate immunity) is dependent on signals transmitted by Tyrosine kinase receptors of the Tyro 3 family (Tyro 3, mer, Axl). The activation pathway(s) responsible for this terminal differentiation are studied.

Collaborators: J. Di Santo, Unité des Cytokines et Développement Lymphoïde, Institut Pasteur, Paris ; D. Raulet, and G. Lemke, Berkeley, CA.


Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
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