The lymphoid lineage–specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells

• DOI: 10.1038/ni.2634
• Publication Date: 2013-06-23T19:48:47Z
• Authors: Yinming Liang; Margot Cucchetti; Romain Roncagalli; Tadashi Yokosuka; Aurélie Malzac; Elodie Bertosio; Jean Imbert; Isaac J Nijman; Miloslav Suchanek; Takashi Saito; Christoph Wülfing; Bernard Malissen; Marie Malissen
• Keywords: Immunological synapse

Although T cell activation can result from signaling via T cell antigen receptor (TCR) alone, physiological T cell responses require costimulation via the coreceptor CD28. Through the use of an N-ethyl-N-nitrosourea-mutagenesis screen, we identified a mutation in Rltpr. We found that Rltpr was a lymphoid cell-specific, actin-uncapping protein essential for costimulation via CD28 and the development of regulatory T cells. Engagement of TCR-CD28 at the immunological synapse resulted in the colocalization of CD28 with both wild-type and mutant Rltpr proteins. However, the connection between CD28 and protein kinase C-θ and Carma1, two key effectors of CD28 costimulation, was abrogated in T cells expressing mutant Rltpr, and CD28 costimulation did not occur in those cells. Our findings provide a more complete model of CD28 costimulation in which Rltpr has a key role.