Giving Form to CTLA-4 Interactions

Science's STKE  31 Oct 2000:
Vol. 2000, Issue 56, pp. tw10
DOI: 10.1126/stke.2000.56.tw10

Signals delivered by cell surface receptor CTLA-4 are critical for ensuring that T cells do not overstep their mark when responding to antigen. How this is accomplished is not fully understood, but it involves -- at least in part --direct inhibitory signals. The efficiency of these signals likely relies on the assembly of inhibitory signaling complexes at the interface between the antigen-presenting cell and the T cell. Ostrov et al. have solved the crystal structure of CTLA-4 and in so doing revealed how the organization of this receptor might facilitate the arrangement of such complexes. Their data suggest that CTLA-4 forms dimers that are unlike those made by other members of the immunolglobulin supergene family in that it can interact simultaneously with two of its natural B7 ligands. This serial organization could help to explain the proficiency of CTLA-4 in regulating the immune responses.

Ostroy, D.A., Shi, W., Schwartz, J.-C.D., Almo, S.C., and Nathenson, S.G. (2000) Structure of murine CTLA-4 and its role in modulating T cell responsiveness. Science 290: 816-819. [Abstract] [Full Text]