Receptors Signaling in Space

L. Bryan Ray

Science, Science Signaling, AAAS, Washington, DC 20005, USA

Shen et al. explored the role of spacing of receptor ligands for activation of T cells. Regions of interaction of T cells with antigen-presenting cells have a distinct spatial organization of membrane components known as the immunological synapse. Shen et al. devised a way to control the spatial distribution of antibodies to the T cell receptor (anti-CD3) and antibodies to the costimulatory receptor CD28 (anti-CD28) on a surface that allowed them to explore the importance of such spatial properties. They used microcontact printing to create a surface in which either anti-CD3 and anti-CD28 were presented together, or anti-CD28 was segregated in dots 1 µm in diameter surrounding anti-CD3 regions. Thus, in the segregated conformation, a 6-µm cell contacted about four of these locations containing anti-CD28. T cells exposed to the surface localized to the antibody-coated regions of the surface regardless of antibody segregation, but secretion of interleukin-2 by mouse CD4⁺ T cells was increased if anti-CD28 was segregated at the periphery of a central locus of anti-CD3 rather than uniformly distributed with the anti-CD3. Activation of the kinase Akt was also greater in cells exposed to the segregated signals, but protein kinase C- colocalized with anti-CD3 in either spatial presentation. The dynamics of cell interaction with the receptors was measured by interference reflection microscopy and revealed that cells transiently contacted and released patches containing segregated anti-CD28 but--because anti-CD3 is not as readily released--remained associated with surfaces where the ligands were mixed. The experimental system may allow further insight into the mechanisms by which the geometry of immunological synapses influences intracellular signaling.

K. Shen, V. K. Thomas, M. L. Dustin, L. C. Kam, Micropatterning of costimulatory ligands enhances CD4⁺ T cell function. Proc. Natl. Acad. Sci. U.S.A. 105, 7791-7796 (2008). [Abstract] [Full Text]