The invention is directed to methods of modulating an immune response in an animal, comprising administering a composition comprising one or more soluble CD1d complexes, in particular non-specific soluble CD1d complexes. Soluble CD1d complexes comprise a soluble CD1d polypeptide, a β2-microglobulin polypeptide, and a ceramide-like glycolipid antigen bound to the CD1d antigen binding groove, and in certain embodiments, an immunogen. The administration of compositions of the present invention affects the activity of CD1d-restricted NKT cells, and in particular, allows for multiple administrations without causing CD1d-restricted NKT cell anergy.
