Complement C1q and CD8+ T cell immunity - implications for autoimmunity. (360G-Wellcome-108008_Z_15_Z)

My overarching hypothesis is that complement C1q modulates CD8+T cell immunity and, by this mechanism, restrains the immune response to self-antigens. Here I propose a series of experimental approaches that will enable me to characterize the mechanism(s) through which C1q regulates CD8+T cell immunity and determine the relevance of these mechanism(s) to patients with systemic lupus erythematosus (SLE). My key research questions are: 1) How does C1q modulate CD8+T cell immunity? 2) Are th e C1q-mediated pathways therapeutically targetable? 3) Is the association between C1q deficiency and SLE the consequence of aberrant CD8+T cell immunity? The combined expertise in studying the biology of the complement system in-vivo and models of autoimmunity/inflammation places my group in a unique position to tackle these important and timely questions.