Diverse patterns of unresponsiveness in an acetylcholine receptor-specific T-cell clone from a myasthenia gravis patient after engaging the T-cell receptor with three different ligands

Using all acetylcholine receptor-specific T-cell clone (TCC) from a myasthenia gravis patient, ive have compared the induction of unresponsiveness by three agents: an anti-V beta monoclonal antibody (mAb). complexes of MHC class II with specific peptide (DR4:peptide) and free peptide. Pretreatment with each agent without antigen-presenting cells specifically rendered the TCC unresponsive to a subsequent optimal stimulus. A substantial proportion of the DR4:peptide pretreated cells underwent apoptosis and the remainder were profoundly unresponsive. Apoptosis was less prominent after pretreatment with free peptide and was not significant with anti-V beta mAb: with both. the unresponsiveness was transient in the survivors. These diverse effects of engaging the T-cell receptor in the absence of costimulation suggest that these agents act via different mechanisms, and give insights into the potential for specific immunotherapy. (C) 1998 Elsevier Science B.V.