LICOS, a primordial costimulatory ligand?

Abstract

In mammals, the classical B7 molecules expressed on antigen-presenting cells, B7-1 (CD80) and B7-2 (CD86), bind the structurally related glycoproteins CD28 and CTLA-4 (CD152), generating costimulatory signals that regulate the activation state of T cells. A recently identified human CD28-like protein, ICOS, also induces costimulatory signals in T cells when crosslinked with antibodies, but it is unclear whether ICOS is part of a B7-mediated regulatory pathway of previously unsuspected complexity, or whether it functions independently and in parallel. Here, we report that, rather than binding B7-1 or B7-2, ICOS binds a new B7-related molecule of previously unknown function that we call LICOS (for ligand of ICOS). At 37 degrees C, LICOS binds only to ICOS but, at lower, non-physiological temperatures, it also binds weakly to CD28 and CTLA-4. Sequence comparisons suggest that LICOS is the homologue of a molecule expressed by avian macrophages and of a murine protein whose expression is induced in non-lymphoid organs by tumour necrosis factor alpha (TNFalpha). Our results define the components of a distinct and novel costimulatory pathway and raise the possibility that LICOS, rather than B7-1 or B7-2, is the contemporary homologue of a primordial vertebrate costimulatory ligand.

ICOS-Induced B7h Shedding on B Cells Is Inhibited by TLR7/8 and TLR9

“…In mouse models of rheumatoid arthritis and systemic lupus erythematosus (SLE), 3 blockade of ICOS-B7h interactions resulted in reduced autoantibodies and disease progression (22,23). Enhanced ICOS levels also are associated with disease progression in human SLE patients (24), as well as the autoimmune phenotype of sanroque mice (25).…”

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

“…IRBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] -immunized C57BL/6 mice were treated with anti-B7RP-1 mAb or control IgG from day -1 to day 7 for the induction phase or from day 8 to day 20 for the effector phase. The administration of anti-B7RP-1 mAb at the induction phase was not effective in terms of clinical ( Fig.…”

“…Unlike CD28, ICOS is not expressed on naive T cells, but induced after T cell activation [10][11][12]. Its ligand B7RP-1 (also known as B7 h, B7-H2, GL50, and LICOS) is constitutively expressed on B cells, macrophages, and dendritic cells [12][13][14][15][16]. Ligation of ICOS on activated T cells by mAb or B7RP-1 fusion protein enhanced cytokine production (IL-4, IL-5, IFN-c, and IL-10), whereas IL-2 production was not clearly enhanced [10,12,17].…”

ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+T cells

“…Two splice variants of human ICOS-L have been described and designated hGL50 (3) and B7-H2͞B7RP-1͞hLICOS (4)(5)(6). Both molecules have an identical extracellular domain but differ at the carboxyl-terminal end of their cytoplasmic regions.…”