Voie d'immunisation et séquence d'administration de l ... - TEL

tel-00827710, version 1 - 29 May 2013
A. Stimulation of the immune response with diverse forms of antigen---------------------------- 53
1) Peptide and protein-based vaccines ------------------------------------------------------------------------ 54
2) Nucleic acid-based vaccines -------------------------------------------------------------------------------- 55
3) Cell-based vaccines ------------------------------------------------------------------------------------------ 56
B. Stimulation of the immune response by adjuvants------------------------------------------------ 60
1) Adjuvants used in therapies --------------------------------------------------------------------------------- 61
2) Adjuvants inducing type I IFN production---------------------------------------------------------------- 61
3) Signaling pathways implicated in type I IFN production ----------------------------------------------- 63
4) Effects of type I IFN ----------------------------------------------------------------------------------------- 64
5) Pleiotropic roles of type I IFN ------------------------------------------------------------------------------ 69
IV. Strategies for assessment of antigen-specific T cells in vivo ----------------------------------- 71
A. Available techniques to study the T cell response in vivo --------------------------------------- 71
1) Current techniques-------------------------------------------------------------------------------------------- 72
2) Recent improvement: tetramer-based enrichment-------------------------------------------------------- 74
B. Conditions of immunization ------------------------------------------------------------------------- 74
1) Antigen form and dose--------------------------------------------------------------------------------------- 74
2) Context of immunization ------------------------------------------------------------------------------------ 75
Research Plan -------------------------------------------------------------------------------------------79
I. Impact of the route of immunization on CD8 + T cell cross-priming--------------------------- 79
II. Defining the optimal timing of adjuvant delivery ------------------------------------------------ 80
Chapter 2: Impact of the route of immunization on CD8 T cell cross-priming -----------81
I. Development of tetramer-based enrichment strategy -------------------------------------------- 86
A. Tetramer-based enrichment -------------------------------------------------------------------------- 86
B. Combination with intracellular staining ------------------------------------------------------------ 88
II. Characterization of the T cell response------------------------------------------------------------- 90
A. Kinetic of CD8 + T cell response--------------------------------------------------------------------- 90
B. Functionality of antigen-specific CD8 + T cells---------------------------------------------------- 94
C. Quality of the T cell response ------------------------------------------------------------------------ 98
D. Memory potential of antigen-specific CD8 + T cells ---------------------------------------------- 99
E. Diversity of antigen-specific CD8 + T cells------------------------------------------------------- 101
1) TCR diversity ------------------------------------------------------------------------------------------------ 101
2) T cell avidity ------------------------------------------------------------------------------------------------- 105
III. Does the efficiency of cross-priming depend on antigen persistence?--------------------- 105
A. Persistence of antigen cross-presentation -------------------------------------------------------- 106
B. Persistence of antigen ------------------------------------------------------------------------------- 107
C. Inhibition of cross-presentation with anti-K b -SIINFEKL antibody--------------------------- 110
Chapter 3: Defining optimal timing for adjuvant delivery ---------------------------------- 113
I. The optimal timing for adjuvant delivery is dependent on the route of immunization-- 115
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