LICOS, a primordial costimulatory ligand?

Brodie D, Collins AV, Iaboni A, Fennelly JA, Sparks LM, Xu XN, van der Merwe PA, Davis SJ. (2000), Curr Biol. 10, 333-6

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.

Key figure: Alignment of selected sequences belonging to the extended B7 subset of the immunoglobulin superfamily

Human (h) and mouse (m) LICOS, chCD80L (EMBL accession number Y08823), B7-1 (EMBL accession number M27533) and B7-2 (EMBL accession number L25259) protein sequences were aligned using the programme PILEUP (Wisconsin Package Version 10.0, Genetics Computer Group, Wisconsin, Madison). Residues that are identical in 5/5 or 4/5 sequences are shaded red and those identical in 3/5 sequences are shaded blue. The hLICOS and B7-1 sequences share 34% and 24% identity with the chCD80L sequence, indicating that hLICOS, rather than B7-1, is more likely to be the human homologue of chCD80L. Conserved cysteines are shaded yellow. The numbers above the alignment refer to the hLICOS sequence. The blue and green lines over the sequences mark the predicted signal peptide and transmembrane domain sequences of hLICOS, respectively.