Cytotoxic T-lymphocyte-associated protein 4
(CTLA-4) is an inhibitory receptor belonging to the CD28 immunoglobulin
subfamily, expressed primarily by T-cells. The family includes CD28, CTLA-4 and
ICOS as well as other proteins including PD-1, BTLA and TIGIT.Its ligands, CD80
and CD86, are typically found on the surface of antigen-presenting cells and
can either bind CD28 or CTLA-4, resulting in a costimulatory or a co-inhibitory
response, respectively. Because of its dampening effect, CTLA-4 is a crucial regulator
of T-cell homeostasis and self-tolerance. The mechanisms by which CTLA-4 exerts
its inhibitory function can be categorized as either cell-intrinsic (affects
the CTLA-4 expressing T-cell) or cell-extrinsic (affects secondary cells).
CTLA-4 mainly acts in a cell-extrinsic manner via its competition with CD28,
CTLA-4-mediated trans-endocytosis of CD80 and CD86, and its direct tolerogenic
effects on the interacting cell.
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