A novel approach to antigen-specific deletion of CTL with minimal cellular activation using α3 domain mutants of MHC class I/peptide complex

Xiao Ning Xu, Marco A. Purbhoo, Nan Chen, Juthathip Mongkolsapaya, Jennifer H. Cox, Ute Christiane Meier, Sabrina Tafuro, P. Rod Rod Dunbar, Andy K. Sewell, Christopher Hourigan, Victor Appay, Vincenzo Cerundolo, Scott R. Burrows, Andrew J. McMichael, Gavin R. Screaton

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)591-602
Number of pages12
JournalImmunity
Volume14
Issue number5
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Xu, X. N., Purbhoo, M. A., Chen, N., Mongkolsapaya, J., Cox, J. H., Meier, U. C., ... Screaton, G. R. (2001). A novel approach to antigen-specific deletion of CTL with minimal cellular activation using α3 domain mutants of MHC class I/peptide complex. Immunity, 14(5), 591-602. https://doi.org/10.1016/S1074-7613(01)00133-9