Molecular, cellular, and immunological studies of inherited human CARMIL2 deficiency – CARMIL2

T cells are central in adaptive immunity. On antigen encounter, the T-cell antigen receptor (TCR) becomes engaged and in concert with context-sensitive co-stimulators, such as CD28, induces T-cell activation, differentiation and function. CD28 signaling was recently shown to relies on the CARMIL2 molecule in mouse and humans. Converging evidences also suggest that CARMIL2 plays CD28-independent functions. The present multidisciplinary project aims at elucidating how CARMIL2 signals in human leukocytes and how its malfunction accounts for a human combined immunodeficiency. To reach that goal, the CARMIL2 project will combine a cohort of CD28 or CARMIL2-deficient patients that is unique in the world with novel interactomics, transcriptomics, and functional genomics tools. Although of fundamental nature, the project should improve our understanding of the molecular mechanisms underpinning human CARMIL2 deficiency clinical phenotypes, paving the way for novel therapeutic options.