Low 2-Dimensional CD4 T Cell Receptor Affinity for Myelin Sets in Motion Delayed Response Kinetics
- Publication Date
- March 07, 2012
- Journal
- PLOS ONE
- Authors
- Kristen M. Rosenthal, Lindsay J. Edwards, Joseph J. Sabatino Jr, Jennifer D. Hood, et al
- Volume
- 7
- Issue
- 3
- Pages
- e32562
- DOI
- https://dx.plos.org/10.1371/journal.pone.0032562
- Publisher URL
- http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0032562
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/22412888
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296730
- Europe PMC
- http://europepmc.org/abstract/MED/22412888
- Web of Science
- 000303060800029
- Scopus
- 84857853669
- Mendeley
- http://www.mendeley.com/research/low-2dimensional-cd4-t-cell-receptor-affinity-myelin-sets-motion-delayed-response-kinetics
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Mendeley | Further Information
{"title"=>"Low 2-dimensional CD4 T cell receptor affinity for myelin sets in motion delayed response kinetics", "type"=>"journal", "authors"=>[{"first_name"=>"Kristen M.", "last_name"=>"Rosenthal", "scopus_author_id"=>"26032351200"}, {"first_name"=>"Lindsay J.", "last_name"=>"Edwards", "scopus_author_id"=>"23484826200"}, {"first_name"=>"Joseph J.", "last_name"=>"Sabatino", "scopus_author_id"=>"24336484800"}, {"first_name"=>"Jennifer D.", "last_name"=>"Hood", "scopus_author_id"=>"24171053900"}, {"first_name"=>"Heather A.", "last_name"=>"Wasserman", "scopus_author_id"=>"35207535000"}, {"first_name"=>"Cheng", "last_name"=>"Zhu", "scopus_author_id"=>"55584801040"}, {"first_name"=>"Brian D.", "last_name"=>"Evavold", "scopus_author_id"=>"7004114695"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"364373839", "doi"=>"10.1371/journal.pone.0032562", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"22412888", "issn"=>"19326203", "scopus"=>"2-s2.0-84857853669", "sgr"=>"84857853669"}, "id"=>"569fc21b-373e-3ae0-af03-affd681be99c", "abstract"=>"T cells recognizing self-peptides that mediate autoimmune disease and those that are responsible for efficacious immunity against pathogens may differ in affinity for antigen due to central and peripheral tolerance mechanisms. Here we utilize prototypical self-reactive (myelin) and viral-specific (LCMV) T cells from T cell receptor (TCR) transgenic mice (2D2 and SMARTA, respectively) to explore affinity differences. The T cells responsive to virus possessed >10,000 fold higher 2D affinity as compared to the self-reactive T cells. Despite their dramatically lower affinity for their cognate ligand, 2D2 T cells respond with complete, albeit delayed, activation (proliferation and cytokine production). SMARTA activation occurs rapidly, achieving peak phosphorylation of p38 (1 minute), Erk (30 minutes), and Jun (3 hours) as well as CD69 and CD25 upregulation (3 and 6 hours, respectively), with a corresponding early initiation of proliferation. 2D2 stimulation with MOG results in altered signaling--no phospho-Erk or phospho-p38 accumulation, significantly delayed activation kinetics of Jun (12 hours), and delayed but sustained SHP-1 activity--as well as delayed CD69 and CD25 expression (12-24 hours), and slow initiation of proliferation. This delay was not intrinsic to the 2D2 T cells, as a more potent antigen with >100-fold increased 2D affinity restored rapid response kinetics in line with those identified for the viral antigen. Taken together, these data demonstrate that time can offset low TCR affinity to attain full activation and suggest a mechanism by which low affinity T cells participate in autoimmune disease.", "link"=>"http://www.mendeley.com/research/low-2dimensional-cd4-t-cell-receptor-affinity-myelin-sets-motion-delayed-response-kinetics", "reader_count"=>17, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>3, "Neuroscience"=>2, "Chemistry"=>1, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Czech Republic"=>1, "United States"=>2, "Germany"=>1}, "group_count"=>1}CrossRef
- http://doi.org/10.1038/ncomms13848
- http://doi.org/10.1111/imr.12122
- http://doi.org/10.1038/nm.3180
- http://doi.org/10.4049/jimmunol.1501407
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- http://doi.org/10.4049/jimmunol.1800295
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- http://doi.org/10.1126/scitranslmed.aao5563
- http://doi.org/10.4049/jimmunol.1501464
- http://doi.org/10.3389/fimmu.2015.00468
- http://doi.org/10.4161/hv.23685
- http://doi.org/10.1016/j.celrep.2018.11.070
- http://doi.org/10.1371/journal.pone.0149582
- http://doi.org/10.3389/fendo.2017.00351
Scopus | Further Information
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Relative Metric
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