A new approach to T-cell activation: Natural and synthetic conjugates capable of activating T cells

T-cell activation and response to antigen follows presentation by major histocompatibility complex (MHC)-compatible antigen-presenting cells (APC). Activation requires a number of separate but interrelated receptor-ligand interactions between the T cell and APC. Some of these interactions can be mimicked by other molecules, such as lectins, antibodies, or synthetic peptides. We discuss the potential use of conjugates to activate T cells, and describe a new class of heteroconjugates for stimulation or modulation of antigen-specific T-cell activity. These heteroconjugates contain an antigen-specific epitope coupled to a T-cell ligand, which replaces some functions of the APC. Such heteroconjugates would bind and supply two signals to T cells, one through the antigen-recognition site of the T-cell receptor and the other through receptors required for activation. Natural heteroconjugates of this type have been identified, for example in a small peptide derived from a Mycobacterium leprae protein.1 Coupling of these two signaling moieties into a single soluble molecule may allow antigen-specific T-cell activation without the need for processing and presentation by antigen-presenting cells and without MHC restriction. Conjugates of this type may be useful for the study of T-cell activation, the development of new antigen-specific diagnostic materials and immunomodulators, and possibly a new class of vaccines.