Natural Ligand of Mouse CD1d1: Cellular Glycosylphosphatidylinositol

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Abstract
Mouse CD1d1, a member of the CD1 family of evolutionarily conserved major histocompatibility antigen–like molecules, controls the differentiation and function of a T lymphocyte subset, NK1 + natural T cells, proposed to regulate immune responses. The CD1d1 crystal structure revealed a large hydrophobic binding site occupied by a ligand of unknown chemical nature. Mass spectrometry and metabolic radiolabeling were used to identify cellular glycosylphosphatidylinositol as a major natural ligand of CD1d1. CD1d1 bound glycosylphosphatidylinositol through its phosphatidylinositol aspect with high affinity. Glycosylphosphatidylinositol or another glycolipid could be a candidate natural ligand for CD1d1-restricted T cells.