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

Autor: Ute-Christiane Meier, P R Dunbar, Marco A. Purbhoo, C. S. Hourigan, Gavin R. Screaton, Xinfang Xu, Andrew K. Sewell, Andrew J. McMichael, Victor Appay, Nan Chen, Juthathip Mongkolsapaya, Vincenzo Cerundolo, J H Cox, S Tafuro, Scott R. Burrows
Jazyk: angličtina
Rok vydání: 2001
Předmět:
Fas Ligand Protein
HIV Antigens
Recombinant Fusion Proteins
Immunology
Receptors
Antigen
T-Cell

Gene Products
gag

Mutagenesis (molecular biology technique)
Apoptosis
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Biology
Lymphocyte Activation
gag Gene Products
Human Immunodeficiency Virus

Fas ligand
HLA-B44 Antigen
Viral Matrix Proteins
Viral Proteins
03 medical and health sciences
0302 clinical medicine
HLA-A2 Antigen
MHC class I
Humans
Cytotoxic T cell
Immunology and Allergy
fas Receptor
Phosphorylation
030304 developmental biology
0303 health sciences
Membrane Glycoproteins
Membrane Proteins
hemic and immune systems
Fas receptor
Molecular biology
Peptide Fragments
CTL
Infectious Diseases
HLA-B Antigens
Influenza A virus
Mutagenesis
biology.protein
Peptides
beta 2-Microglobulin
Ex vivo
CD8
T-Lymphocytes
Cytotoxic

030215 immunology
Zdroj: Immunity. 14(5)
ISSN: 1097-4180
1074-7613
Popis: 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.
Databáze: OpenAIRE