Gallimore, A., Glithero, A., Godkin, Andrew James  ORCID: https://orcid.org/0000-0002-1910-7567, 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.
|
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: | 27 Oct 2022 10:11 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/69217 |
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