Inducible T-cell costimulator–Inducible T-cell costimulator ligand interface (ICOSL–ICOS interface)

The ICOS–ICOSL interface is a critical costimulatory signaling axis within the CD28–B7 superfamily, primarily responsible for modulating adaptive immune responses. ICOS (Inducible T-cell costimulator, CD278) is upregulated on T cells following initial activation, while its ligand, ICOSL (B7-H2, CD275), is constitutively or inducibly expressed on B cells and other antigen-presenting cells. The physical interaction between these two proteins is essential for the differentiation of T follicular helper (Tfh) cells and the subsequent formation of germinal centers, which are vital for high-affinity antibody production and B-cell memory. In oncology, the interface is targeted by agonist antibodies to bolster the activity of cytotoxic T cells against tumors, whereas in autoimmune diseases, antagonists are used to disrupt the pathway and reduce pathogenic autoantibody production. Because ICOS is also highly expressed on regulatory T cells (Tregs), therapeutic modulation of this interface requires careful calibration to balance effector T-cell stimulation against potential immune suppression.

Other names

CD278–CD275 interactionB7-H2–ICOS interactionB7RP-1–ICOS interactionICOS–ICOSLG complexICOS–B7-H2 pathway

Competitive inhibition of the ICOS-ICOSL binding interface to suppress T-cell-mediated autoimmunity; Agonistic stimulation of the ICOS receptor to enhance anti-tumor T-cell activity; Dual blockade of ICOS and CD28 pathways to inhibit costimulation.