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dc.contributor.authorLucas, Julie Ann
dc.contributor.authorAtherly, Luana O.
dc.contributor.authorBerg, Leslie J.
dc.date2022-08-11T08:09:01.000
dc.date.accessioned2022-08-23T16:15:36Z
dc.date.available2022-08-23T16:15:36Z
dc.date.issued2002-06-11
dc.date.submitted2008-11-05
dc.identifier.citation<p>J Immunol. 2002 Jun 15;168(12):6142-51.</p>
dc.identifier.issn0022-1767 (Print)
dc.identifier.doi10.4049/jimmunol.168.12.6142
dc.identifier.pmid12055226
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34129
dc.description.abstractThe Tec family tyrosine kinase Itk is critical for efficient signaling downstream of the TCR. Biochemically, Itk is directly phosphorylated and activated by Lck. Subsequently, Itk activates phospholipase C-gamma1, leading to calcium mobilization and extracellular signal-regulated kinase/mitogen-activated protein kinase activation. These observations suggested that Itk might play an important role in positive selection and CD4/CD8 lineage commitment during T cell development in the thymus. To test this, we crossed Itk-deficient mice to three lines of TCR transgenics and analyzed progeny on three different MHC backgrounds. Analysis of these mice revealed that fewer TCR transgenic T cells develop in the absence of Itk. In addition, examination of multiple T cell development markers indicates that multiple stages of positive selection are affected by the absence of Itk, but the T cells that do develop appear normal. In contrast to the defects in positive selection, CD4/CD8 lineage commitment seems to be intact in all the TCR transgenic itk(-/-) lines tested. Overall, these data indicate that altering TCR signals by the removal of Itk does not affect the appropriate differentiation of thymocytes based on their MHC specificity, but does impact the efficiency with which thymocytes complete their maturation process.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12055226&dopt=Abstract">Link to article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.4049/jimmunol.168.12.6142
dc.subjectAnimals; Antigen-Presenting Cells; *Antigens, CD; Antigens, CD4; Antigens, CD5; Biological Markers; Cell Differentiation; Cell Lineage; Dose-Response Relationship, Immunologic; Down-Regulation; H-2 Antigens; Ligands; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell, alpha-beta; *Receptors, Immunologic; Signal Transduction; T-Lymphocyte Subsets; Thymus Gland; Transgenes
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleThe absence of Itk inhibits positive selection without changing lineage commitment
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume168
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/791
dc.identifier.contextkey661901
html.description.abstract<p>The Tec family tyrosine kinase Itk is critical for efficient signaling downstream of the TCR. Biochemically, Itk is directly phosphorylated and activated by Lck. Subsequently, Itk activates phospholipase C-gamma1, leading to calcium mobilization and extracellular signal-regulated kinase/mitogen-activated protein kinase activation. These observations suggested that Itk might play an important role in positive selection and CD4/CD8 lineage commitment during T cell development in the thymus. To test this, we crossed Itk-deficient mice to three lines of TCR transgenics and analyzed progeny on three different MHC backgrounds. Analysis of these mice revealed that fewer TCR transgenic T cells develop in the absence of Itk. In addition, examination of multiple T cell development markers indicates that multiple stages of positive selection are affected by the absence of Itk, but the T cells that do develop appear normal. In contrast to the defects in positive selection, CD4/CD8 lineage commitment seems to be intact in all the TCR transgenic itk(-/-) lines tested. Overall, these data indicate that altering TCR signals by the removal of Itk does not affect the appropriate differentiation of thymocytes based on their MHC specificity, but does impact the efficiency with which thymocytes complete their maturation process.</p>
dc.identifier.submissionpathgsbs_sp/791
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentProgram in Immunology and Virology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages6142-51


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