Stable, soluble T-cell receptor molecules for crystallization and therapeutics

Antibody and T-cell receptors (TCRs) are the primary recognitionmolecules of the adaptive immune system. Antibodies have beenextensively characterized and are being developed for a largenumber of therapeutic applications. This has been possible becauseof the ability to manufacture stable, soluble, monoclonal antibodieswhich retain the antigen specificity of B cells. Unlike antibodies,TCRs are not expressed in a soluble form, but are anchored tothe T-cell surface by an insoluble trans-membrane domain. Characterizationand development of TCRs has been hampered by the lack of suitablemethods for producing them as soluble and stable proteins. Herewe report the engineering of soluble human TCRs suitable forcrystallization studies and potentially for in vivo therapeuticuse. Received March 11, 2003; revised July 1, 2003; accepted July 30, 2003.