Cis interactions between CD2 and its ligands on T cells are required for T cell activation

Bin Li (1, 2) , Yan Lu (1) , Ming-Chao Zhong (1) , Jin Qian (1) , Rui Li (1, 3) , Dominique Davidson (1) , Zhenghai Tang (1) , Kaiwen Zhu (1, 3) , Jérémy Argenty (4) , Anne Gonzalez de Peredo (5) , Bernard Malissen (4, 6) , Romain Roncagalli (4) , André Veillette (1, 2, 3)

1 IRCM - Institut de Recherches Cliniques de Montréal
2 UQAM - Université du Québec à Montréal = University of Québec in Montréal
3 McGill University = Université McGill [Montréal, Canada]
4 CIML - Centre d'Immunologie de Marseille - Luminy
5 IPBS - Institut de pharmacologie et de biologie structurale
6 CIPHE - Centre d'Immunophénomique

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.

Domaines: Sciences du Vivant [q-bio]

Bin Li, Yan Lu, Ming-Chao Zhong, Jin Qian, Rui Li, et al.. Cis interactions between CD2 and its ligands on T cells are required for T cell activation. Science Immunology, 2022, 7 (74), ⟨10.1126/sciimmunol.abn6373⟩. ⟨hal-03867882⟩