TY - JOUR
T1 - A novel approach to antigen-specific deletion of CTL with minimal cellular activation using α3 domain mutants of MHC class I/peptide complex
AU - Xu, Xiao Ning
AU - Purbhoo, Marco A.
AU - Chen, Nan
AU - Mongkolsapaya, Juthathip
AU - Cox, Jennifer H.
AU - Meier, Ute Christiane
AU - Tafuro, Sabrina
AU - Rod Dunbar, P. Rod
AU - Sewell, Andy K.
AU - Hourigan, Christopher S.
AU - Appay, Victor
AU - Cerundolo, Vincenzo
AU - Burrows, Scott R.
AU - McMichael, Andrew J.
AU - Screaton, Gavin R.
N1 - Funding Information:
We thank Dr. T. Hansasuta for expert help with tetramer and Ig fusion proteins; Drs. N. Wilcox, D. Jackson, G. Gao, K. Simon, and C. Bangham for discussions; and Dr. S. Nagata for anti-FasL mAb. This work was supported by the Medical Research Council and Wellcome Trust, United Kingdom.
PY - 2001
Y1 - 2001
N2 - In this study, we have compared the effector functions and fate of a number of human CTL clones in vitro or ex vivo following contact with variant peptides presented either on the cell surface or in a soluble multimeric format. In the presence of CD8 coreceptor binding, there is a good correlation between TCR signaling, killing of the targets, and FasL-mediated CTL apoptosis. Blocking CD8 binding using α3 domain mutants of MHC class I results in much reduced signaling and reduced killing of the targets. Surprisingly, however, FasL expression is induced to a similar degree on these CTLs, and apoptosis of CTL is unaffected. The ability to divorce these events may allow the deletion of antigen-specific and pathological CTL populations without the deleterious effects induced by full CTL activation.
AB - In this study, we have compared the effector functions and fate of a number of human CTL clones in vitro or ex vivo following contact with variant peptides presented either on the cell surface or in a soluble multimeric format. In the presence of CD8 coreceptor binding, there is a good correlation between TCR signaling, killing of the targets, and FasL-mediated CTL apoptosis. Blocking CD8 binding using α3 domain mutants of MHC class I results in much reduced signaling and reduced killing of the targets. Surprisingly, however, FasL expression is induced to a similar degree on these CTLs, and apoptosis of CTL is unaffected. The ability to divorce these events may allow the deletion of antigen-specific and pathological CTL populations without the deleterious effects induced by full CTL activation.
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U2 - 10.1016/S1074-7613(01)00133-9
DO - 10.1016/S1074-7613(01)00133-9
M3 - Article
C2 - 11371361
AN - SCOPUS:0035017468
VL - 14
SP - 591
EP - 602
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 5
ER -