Moving CTLA-4 from the trash to recycling

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Science  24 Jul 2015:
Vol. 349, Issue 6246, pp. 377-378
DOI: 10.1126/science.aac7888

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To prevent immune responses to our own bodies, a series of immune checkpoints exist. Cytotoxic T lymphocyte antigen–4 (CTLA-4) operates the earliest checkpoint controlling whether or not T cells respond to antigen. Manipulation of CTLA-4 has recently gained enormous attention in the field of tumor immunotherapy (1). However, in its day-to-day activities, CTLA-4 prevents autoimmune targeting of tissues (2), though the precise mechanism of action and critical controls influencing CTLA-4 function are still emerging. On page 436 in this issue, Lo et al. (3) provide evidence that an intracellular protein, lipopolysaccharide-responsive and beige-like anchor protein (LRBA) controls CTLA-4 expression and thereby influences immune self-tolerance.