细胞免疫T细胞活化的分子机制 硕士.pptVIP

第二代抗体之二：抗肿瘤单克隆抗体(PD-1/PD-L1 mAb) Anti-PD-1 mAb Anti-PD-L1 mAb The activation of CD8+ T cells Require both antigen recognition and second signals May require second signal provided by CD4 Th cells in the conditions that tend to elicit weak innate immune reactions latent viral infection organ transplants tumor Role of co-stimulation and helper T cells in the CD8+ T cell differentiation Hierarchical T cell exhaustion during chronic infection Subsets of exhausted T cells and combinatorial strategies to reverse exhaustion Acuto O, VD Bartolo, and F Michel. Tailoring T-cell receptor signals by proximal negative feedback mechanisms. Nature Reviews Immunology 8:699-712, 2008. Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nature Reviews Immunology 4:336-347, 2004. Greenwald RJ, GJ Freeman, and AH Sharpe. The B7 family revisited. Annual Review of Immunology 23:515-548, 2005. Huse M, EJ Quann, and MM Davis. Shouts, whispers and the kiss of death: directional secretion in T cells. Nature Immunology 9:1105-1111, 2008. Seder RA, and R Ahmed. Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nature Immunology 4:835-842, 2003 Chen L and Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nature Reviews Immunology 12:227-242, 2013 Wherry, E. J. T cell exhaustion. Nature Immunol. 12,492–499 (2011). Williams MA, and MJ Bevan. Effector and memory CTL differentiation. Annual Review of Immunology 25:171-192, 2007. Selected readings * * * * * * * * * * * * Signal 1 TCR - MHC+Ag interaction not enough for full activation Overview of TCR signalling Nature Review Immunol 2013 three major signalling pathways Provided by Costimulatory Molecules on activated APCs APC T Cell B7 CD28 Signal 2 B7.1 (CD80) B7.2 (CD86) promote the survival and expansion of the T cells A comparison between signalling pathways in fully stimulated and in anergized T cells de