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 an acetylcholine receptor-specific T-cell clone (TCC) from a myasthenia gravis patient, we 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 to the potential for specific immunotherapy.
Bond
A P
AP
Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, UK.
Corlett
L
L
Curnow
S J
SJ
Spack
E
E
Willcox
N
N
Newsom-Davis
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D009157:Myasthenia Gravis / Q000378:metabolism* / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011950:Receptors, Cholinergic