Signal Stealer

Science Signaling  03 May 2011:
Vol. 4, Issue 171, pp. ec125
DOI: 10.1126/scisignal.4171ec125

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is expressed by activated and regulatory T cells and helps to prevent T cell–mediated immune responses from getting out of control. The costimulatory pair of ligands bind CTLA-4 and are expressed on antigen-presenting cells. CD80 and CD86 also bind to CD28 expressed on T cells, which is critical for T cell activation. Qureshi et al. (see the Perspective by Sakaguchi and Wing) find that CTLA-4, expressed by both human and mouse T cells, plucks CD80 and CD86 from the surface of antigen-presenting cells and internalizes them through trans-endocytosis. These findings suggest an extrinsic cell mechanism for the negative regulation of T cell immunity by CTLA-4.

O. S. Qureshi, Y. Zheng, K. Nakamura, K. Attridge, C. Manzotti, E. M. Schmidt, J. Baker, L. E. Jeffery, S. Kaur, Z. Briggs, T. Z. Hou, C. E. Futter, G. Anderson, L. S. K. Walker, D. M. Sansom, Trans-endocytosis of CD80 and CD86: A molecular basis for the cell-extrinsic function of CTLA-4. Science 332, 600–603 (2011). [Abstract] [Full Text]

S. Sakaguchi, K. Wing, Damping by depletion. Science 332, 542–543 (2011). [Abstract] [Full Text]