A novel approach to antigen-specific deletion of CTL with minimal cellularactivation using alpha 3 domain mutants of MHC class I/peptide complex

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 pep tides presented either on the cell surface or in a soluble multimeric forma t. In the presence of CD8 coreceptor binding, there is a good correlation b etween TCR signaling, killing of the targets, and Fast-mediated CTL apoptos is. Blocking CD8 binding using (alpha3 domain mutants of MHC class I result s in much reduced signaling and reduced killing of the targets. Surprisingl y, however, Fast expression is induced to a similar degree on these CTLs, a nd apoptosis of CTL is unaffected. The ability to divorce these events may allow the deletion of antigen-specific and pathological CTL populations wit hout the deleterious effects induced by full CTL activation.