DIVERSE PATTERNS OF UNRESPONSIVENESS IN AN ACETYLCHOLINE RECEPTOR-SPECIFIC T-CELL CLONE FROM A MYASTHENIA-GRAVIS PATIENT AFTER ENGAGING THET-CELL RECEPTOR WITH 3 DIFFERENT LIGANDS

Using all acetylcholine receptor-specific T-cell clone (TCC) from a my asthenia gravis patient, ive have compared the induction of unresponsi veness by three agents: an anti-V beta monoclonal antibody (mAb). comp lexes of MHC class II with specific peptide (DR4:peptide) and free pep tide. Pretreatment with each agent without antigen-presenting cells sp ecifically rendered the TCC unresponsive to a subsequent optimal stimu lus. A substantial proportion of the DR4:peptide pretreated cells unde rwent apoptosis and the remainder were profoundly unresponsive. Apopto sis was less prominent after pretreatment with free peptide and was no t significant with anti-V beta mAb: with both. the unresponsiveness wa s transient in the survivors. These diverse effects of engaging the T- cell receptor in the absence of costimulation suggest that these agent s act via different mechanisms, and give insights into the potential f or specific immunotherapy. (C) 1998 Elsevier Science B.V.