LICOS, a primordial costimulatory ligand?

Curr Biol. 2000 Mar 23;10(6):333-6. doi: 10.1016/s0960-9822(00)00383-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • Base Sequence
  • Cell Line, Transformed
  • DNA, Complementary
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Ligands
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Sequence Homology, Amino Acid
  • Surface Plasmon Resonance / methods

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • DNA, Complementary
  • ICOS protein, human
  • ICOSLG protein, human
  • Icos protein, mouse
  • Icosl protein, mouse
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Ligands
  • Membrane Glycoproteins
  • Proteins
  • Receptors, Antigen, T-Cell

Associated data

  • GENBANK/AB014553