Current Literature: Redistribution of lipid rafts by CD28 costimulation.

Abstract

Viola, A., Schroeder, S., Sakakibara, Y. and Lanzavecchia, A. (1999) T lymphocyte costimulation mediated by reorganization of membrane microdomains Science 283, 680–682TCR stimulation is regulated by engagement with the costimulatory molecule CD28. Here, Viola et al. demonstrate that CD28 engagement led to the redistribution and clustering of membrane and intracellular kinase-rich raft microdomains at the TCR contact site.Human resting T cells were stimulated with beads coated with antibody to CD3 with or without anti-CD28. CD28 ligation was shown to increase the T-cell response as well as early tyrosine phosphorylation. This effect was not due to more TCRs being triggered, as the same number of TCR/CD3 complexes were downregulated with or without CD28 costimulation.Tyrosine phosphorylation was rapidly lost as soon as kinases were inhibited, but in the presence of CD28 costimulation, showed greater stability. In addition, CD28 engagement was shown to increase degradation of Lck, indicating an increase in kinase recruitment and consumption by the same number of TCRs.The effect of CD28 on TCR-induced Lck consumption and substrate phosphorylation was investigated by analysing whether CD28 engagement affects the distribution of the plasma membrane lipid microdomains, or rafts. In unstimulated resting T cells, and T cells stimulated with anti-CD3 alone the rafts were evenly distributed on the surface, however, after stimulation with anti-CD3 plus anti-CD28 the rafts aggregated in the TCR contact area.CD28 thus plays a role in the organization of the immune synapse by recruiting rafts into it. This might represent a general mechanism by which costimulation can increase the signaling process.