florence faure PhD Immunology
Course and current status
POSITION : Scientist in Immunolgy (Permanent position CRI) - INSERM
INSERM U932, Institut Curie, 12 rue Lhomond, Paris 75005 France
LAB EXPERIENCES :
1984 : Institut de Microbiologie, Université Paris-Sud - Orsay
- Tn 7 Transposon
1985 : Laboratoire d'Immunogénétique de la Transplantation
INSERM U93, Hôpital Saint-Louis, Paris
- IL3 production by PBL from BMT patients
1986-90 : INSERM U333, Institut Gustave-Roussy, Villejuif
- Characterization of human TCR gamma/delta+ lymphocytes
- Study of MHC-independent interaction between T lymphocyte and target cell
1991 : Laboratoire du Pr C. Milstein, LMB, MRC, Cambridge, U.K.
- Functional and biochemical characterization of human CD1 molecules
1992-96 : Unité INSERM 333, Institut Gustave Roussy, Villejuif.
- Involvement of LAG-3 receptor in T cell interactions
- Tumor-specific T lymphocyte response in melanoma patients
1997-April 1998 : Unité INSERM 277, Institut Pasteur, Paris
- Tumor-specific T lymphocyte response in melanoma patients
Since April 1998 : Unité INSERM (520/653/932), Institut Curie, Paris
- Antigen presentation and tumor-specific T lymphocyte response in melanoma patients
- Tumor-specific T cell immune response in breast cancer patients
- Cross-presentation of melanoma antigens by human Ag-presenting cells
Scientific summary
Cross-presentation of melanoma antigens by human Ag-presenting cells
Using a simple in vitro assay with human tumor-specific CD8+ T cell clones, we had previously shown that when DCs actively cross present antigens (synthetic 25–30 amino-acid long polypeptides), they are competent for antigen presentation for extended time periods (several days). In contrast, when DCs were pulsed with the minimal MHC class I-binding peptides (8-10 amino-acid long), DCs stimulated the T cell clones effectively during the first day after pulsing, but their antigen presentation capacity dropped dramatically thereafter. Those results obtained both for MelanA/ MART-1 and gp100 long peptides, are comparable for soluble or particulate Ag.
Our current study indicates that the long lasting capacity of DC to stimulate T cells when the Ag is delivered as long peptide is also occurring for monocytes while they differentiate into DC. In addition, we show that Ag uptaken by monocytes is stored intracellularly during differentiation and still available laterly for MHC I loading by Mo-DC. We are currently studying the cell biology of this long lasting Ag cross-presentation and the signals able to modulate it, as assessed by the modulation of CD8 T cell response.
An increasing amount of reports indicate that in inflammatory situation, lymph node DCs might arise from the differentiation of monocytes in non lymphoid organs, and that this pathway may have a major role in the induction of protective CD4 and CD8 responses. It is of special interest to understand the mechanisms allowing cells which uptake Ag in tissue to maintain cross-presentation capacity until Ag-specific T cell encounter and to characterize the signals able to trigger this “late” T cell stimulation.
