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Here, we provide a comprehensive, step\u2010by\u2010step guide to investigate CD8 T cells in murine\n                    <jats:italic>in vivo<\/jats:italic>\n                    lymphocytic choriomeningitis virus (LCMV) infection models. We outline viral stock preparation, infection, and viral titer evaluation. We put an emphasis on flow cytometry as a method to investigate phenotypical and functional characteristics of CD8 T cell exhaustion, but the protocols provided will also facilitate imaging or transcriptomic analyses. With these resources, we aim to streamline establishment of the LCMV model for new users and to support harmonization and optimization of workflows for laboratories already working with this model. \u00a9 2026 The Author(s).\n                    <jats:italic>Current Protocols<\/jats:italic>\n                    published by Wiley Periodicals LLC.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 1<\/jats:bold>\n                    : Virus production\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 2<\/jats:bold>\n                    : Virus titer quantification from virus stocks by focus\u2010forming assay\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Alternate Protocol 1<\/jats:bold>\n                    : Virus titer quantification from infected tissues by focus\u2010forming assay\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 3<\/jats:bold>\n                    : Peptide\u2010MHC\u2010I tetramer production\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 4<\/jats:bold>\n                    : Na\u00efve CD8 T cell isolation using StemCell\n                    <jats:sup>TM<\/jats:sup>\n                    kit\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Alternate Protocol 2<\/jats:bold>\n                    : Na\u00efve CD8 T cell enrichment using MojoSort\n                    <jats:sup>TM<\/jats:sup>\n                    kit\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 5<\/jats:bold>\n                    : Adoptive CD8 T cell transfer and LCMV infection\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 6<\/jats:bold>\n                    : Animal husbandry\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 7<\/jats:bold>\n                    : Preparation of single\u2010cell suspension from secondary lymphoid organs\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Alternate Protocol 3<\/jats:bold>\n                    : Preparation of single\u2010cell suspension from peripheral tissues\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 8<\/jats:bold>\n                    : Extracellular and intracellular staining\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 9<\/jats:bold>\n                    : Restimulation analysis\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 10<\/jats:bold>\n                    : Sorting\n                  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