A novel approach to antigen-specific deletion of CTL with minimal cellular activation using alpha3 domain mutants of MHC class I/peptide complex.

Journal article

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.

Authors: Xu, X; Purbhoo, M; Chen, N; Mongkolsapaya, J; Cox, J

• Publication status: Published
• Journal: Immunity
• Volume: 14
• Issue: 5
• Pages: 591-602
• Publication date: 2001-05-01
• DOI: 10.1016/s1074-7613(01)00133-9
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: Peptides; gag Gene Products, Human Immunodeficiency Virus; Peptide Fragments; Viral Matrix Proteins; HLA-B Antigens; T-Lymphocytes, Cytotoxic; Gene Products, gag; beta 2-Microglobulin; CD8-Positive T-Lymphocytes; Mutagenesis; Fas Ligand Protein; Viral Proteins; Antigens, CD95; Humans; HLA-A2 Antigen; Phosphorylation; Receptors, Antigen, T-Cell; Membrane Proteins; Lymphocyte Activation; HIV Antigens; Apoptosis; Influenza A virus; Recombinant Fusion Proteins; Membrane Glycoproteins