Identification of an Alternative CTLA-4 Ligand Costimulatory for T Cell Activation

TLDR

T cell proliferation requires two signals: antigen recognition by the T cell receptor and a costimulatory signal from a receptor‑ligand pair, such as the CD28–B7 interaction. The authors discovered GL1, a B‑cell surface protein distinct from B7, which serves as the main ligand for CTLA‑4 on activated B cells and delivers a crucial signal for T‑cell‑dependent responses both in vitro and in vivo.

Abstract

Stimulation of T cell proliferation generally requires two signals: The first signal is provided by the T cell receptor binding to antigen, and the second signal or costimulus is provided by a different receptor-ligand interaction. In mouse and human, the CD28-B7 interaction has been identified as a source of costimulatory signals. We have identified a cell surface molecule (GL1) that is distinct from B7 and abundantly expressed on activated B cells. On activated B cells GL1, rather than B7, is the predominant ligand for the T cell-activation molecule CTLA-4. GL1 provides a critical signal for T cell-dependent responses in vitro and in vivo.