{Reference Type}: Journal Article
{Title}: Cis interactions between CD2 and its ligands on T cells are required for T cell activation.
{Author}: Li B;Lu Y;Zhong MC;Qian J;Li R;Davidson D;Tang Z;Zhu K;Argenty J;de Peredo AG;Malissen B;Roncagalli R;Veillette A;
{Journal}: Sci Immunol
{Volume}: 7
{Issue}: 74
{Year}: 08 2022 5
{Factor}: 30.63
{DOI}: 10.1126/sciimmunol.abn6373
{Abstract}: CD2 is largely described to promote T cell activation when engaged by its ligands, CD48 in mice and CD58 in humans, that are present on antigen-presenting cells (APCs). However, both CD48 and CD58 are also expressed on T cells. By generating new knockout mouse strains lacking CD2 or CD48 in the C57BL/6 background, we determined that whereas CD2 was necessary on T cells for T cell activation, its ligand CD48 was not required on APCs. Rather, CD48 was also needed on T cells. One exception was during cytotoxicity, which required CD48 on T cells and APCs. Fluorescence resonance energy transfer (FRET) studies in nonimmune cells provided evidence that cis interactions between CD2 and CD48 existed within individual cells. CD2-CD48 interactions on T cells enabled more robust T cell receptor (TCR) signals, including protein tyrosine phosphorylation. Using T cells from a CD2 knock-in mouse in which a tag was inserted at the carboxyl terminus of CD2, mass spectrometry analyses revealed that the role of CD2 in T cell activation correlated with its ability to interact with components of the TCR complex and the protein tyrosine kinase Lck. CD2-CD58 provided a similar function in human T cells. Thus, our data imply that T cell-intrinsic cis interactions of CD2 with its ligands are required for TCR signaling and T cell activation. Interactions with ligands on APCs contribute during cytotoxicity.