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Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes

Gallimore, A., Glithero, A., Godkin, Andrew James, Tissot, A. C., Plückthun, A., Elliott, T., Hengartner, H. and Zinkernagel, R. 1998. Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. Journal of Experimental Medicine 187 (9) , pp. 1383-1393.

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Abstract

This study describes the construction of soluble major histocompatibility complexes consisting of the mouse class I molecule, H-2Db, chemically biotinylated beta2 microglobulin and a peptide epitope derived from the glycoprotein (GP; amino acids 33-41) of lymphocytic choriomeningitis virus (LCMV). Tetrameric class I complexes, which were produced by mixing the class I complexes with phycoerythrin-labeled neutravidin, permitted direct analysis of virus-specific cytotoxic T lymphocytes (CTLs) by flow cytometry. This technique was validated by (a) staining CD8+ cells in the spleens of transgenic mice that express a T cell receptor (TCR) specific for H-2Db in association with peptide GP33-41, and (b) by staining virus-specific CTLs in the cerebrospinal fluid of C57BL/6 (B6) mice that had been infected intracranially with LCMV-DOCILE. Staining of spleen cells isolated from B6 mice revealed that up to 40% of CD8(+) T cells were GP33 tetramer+ during the initial phase of LCMV infection. In contrast, GP33 tetramers did not stain CD8+ T cells isolated from the spleens of B6 mice that had been infected 2 mo previously with LCMV above the background levels found in naive mice. The fate of virus-specific CTLs was analyzed during the acute phase of infection in mice challenged both intracranially and intravenously with a high or low dose of LCMV-DOCILE. The results of the study show that the outcome of infection by LCMV is determined by antigen load alone. Furthermore, the data indicate that deletion of virus-specific CTLs in the presence of excessive antigen is preceded by TCR downregulation and is dependent upon perforin.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Animals, CD8-Positive T-Lymphocytes/immunology, Flow Cytometry, Glycoproteins/immunology, Histocompatibility Antigens Class I/immunology, Interferon-gamma/analysis, Lymphocytic choriomeningitis virus/chemistry, Lymphocytic choriomeningitis virus/immunology, Major Histocompatibility Complex/immunology, Membrane Glycoproteins/deficiency, Mice, Mice Transgenic, Peptides/immunology, Perforin, Pore Forming Cytotoxic Proteins, Protein Conformation, Receptors, Antigen, T-Cell/physiology, Spleen/immunology, T-Lymphocytes, Cytotoxic/immunology, T-Lymphocytes, Cytotoxic/virology, beta 2-Microglobulin/metabolism
Publisher: Rockefeller University Press
ISSN: 0022-1007
Related URLs:
Last Modified: 04 Jun 2017 07:52
URI: http://orca.cf.ac.uk/id/eprint/69217

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