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Antigen-specific CD8 cells and MHC-peptide tetramers |
Hématologie. Volume 7, Number 4, 251-9, Juillet - Août 2001, Revues
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Résumé
Article gratuit
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Author(s) : Lucile Mollet, Brigitte Autran |
Summary : The new technology of MHC-peptide tetramers, by allowing an easy quantification of cytotoxic T-lymphocytes (CTL) specific for viruses or tumors, has introduced a revolution in the hazardous, tedious and lab-intensive methods previously used to quantify CTL. Not only our understanding of the immune responses to viruses such as HIV, EBV, CMV, HCV... or tumors has been profoundly influenced by this new method, but also some fundamental concepts of basic immunology have been revisited. Tetramer complexes of MHC-class I chains loaded with the index peptide directly bind to cell-surface membrane T-cell receptors. When conjugated to a fluorochrom, tetramers provide a unique method to directly quantify ex vivo, without any in vitro bias, populations of CTL specific for known antigens, to define their phenotypic characteristics, to analyze their functional status or to sort them. The sensitivity of the method allows to detect down to one cell amongs 5 000. These tetramers have thus allowed to directly quantify virus-specific CTL and to demonstrate the basic phenomenon of clonal exhaustion or to eliminate the previous hypothesis of a major bystander activation during viral infections (both in murine models and in human viral infectious) by demonstrating the correlation between the in vivo expansion of virus-specific T-cells and the initial virus burst. Magic tools, tetramers allow major advances in our understanding of CD8 cells in basic biomedical research as well as in clinical research and in the development of diagnostic, therapeutic or vaccine strategies. |
Keywords : cytotoxic T lymphocyte, CTL, MHC-peptide tetramer. |
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