Interactomics of the RLTPR protein explain its essential role for costimulation via CD28

The RLTPR cytosolic protein has an essential role in CD28 costimulation but its mode of action and importance in human T cells remain elusive. Here, using mass spectrometry we showed that CD28, RLTPR and the CARMA1 cytosolic adaptor physically associate in mouse T cells. Although RLTPR is thought to function as an actin-uncapping protein, this property was dispensable for CD28 costimulation. Our findings underpin the convergent function of RLTPR in T cells and suggest that its scaffolding role predominates during CD28 costimulation.