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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 alpha3 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.

Type

Journal article

Journal

Immunity

Publication Date

05/2001

Volume

14

Pages

591 - 602

Keywords

Antigens, CD95, Apoptosis, CD8-Positive T-Lymphocytes, Fas Ligand Protein, Gene Products, gag, HIV Antigens, HLA-A2 Antigen, HLA-B Antigens, HLA-B44 Antigen, Humans, Influenza A virus, Lymphocyte Activation, Membrane Glycoproteins, Membrane Proteins, Mutagenesis, Peptide Fragments, Peptides, Phosphorylation, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, T-Lymphocytes, Cytotoxic, Viral Matrix Proteins, Viral Proteins, beta 2-Microglobulin, gag Gene Products, Human Immunodeficiency Virus