{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:24:54Z","timestamp":1789856694878,"version":"4.0.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR signaling by activating an alternative pathway that is independent of LCK and utilizes a G\u03b111-containing G protein\u2013coupled receptor (GPCR) leading to PLC\u03b2 activation. The molecules linking the superantigen to GPCR signaling are unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, the \u03b12 subunit of the extracellular matrix protein laminin, as the coreceptor for staphylococcal superantigens. Complementary binding assays (ELISA, pull-downs, and surface plasmon resonance) provided direct evidence of the interaction between staphylococcal enterotoxin E and LAMA2. Through its G4 domain, LAMA2 mediated the LCK-independent T cell activation by these toxins. Such a coreceptor role of LAMA2 involved a GPCR of the calcium-sensing receptor type because the selective antagonist NPS 2143 inhibited superantigen-induced T cell activation in vitro and delayed the effects of toxic shock syndrome in vivo. Collectively, our data identify LAMA2 as a target of antagonists of staphylococcal superantigens to treat toxic shock syndrome.<\/jats:p>","DOI":"10.4049\/jimmunol.1701212","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T17:50:23Z","timestamp":1516038623000},"page":"1471-1479","source":"Crossref","is-referenced-by-count":17,"title":["Staphylococcal Superantigens Use LAMA2 as a Coreceptor To Activate T Cells"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-3652","authenticated-orcid":false,"given":"Zhigang","family":"Li","sequence":"first","affiliation":[{"name":"Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University , Montreal, Quebec H3A 2B4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-4793","authenticated-orcid":false,"given":"Joseph J","family":"Zeppa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University , London, Ontario N6A 5C1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Hancock","sequence":"additional","affiliation":[{"name":"Surface Plasmon Resonance\u2013Mass Spectrometry Facility, McGill University , Montreal, Quebec H3G 1Y6,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3742-7289","authenticated-orcid":false,"given":"John K","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University , London, Ontario N6A 5C1,","place":["Canada"]},{"name":"Lawson Health Research Institute , London, Ontario N6A 5C1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1860-4104","authenticated-orcid":false,"given":"Terence M","family":"Doherty","sequence":"additional","affiliation":[{"name":"Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center , Torrance, CA 90277"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8050-1192","authenticated-orcid":false,"given":"Geoffrey N","family":"Hendy","sequence":"additional","affiliation":[{"name":"Metabolic Disorders and Complications, Research Institute of the McGill University Health Centre, and Departments of Medicine, Physiology, and Human Genetics, McGill University , Montreal, Quebec H4A 3J1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6191-3733","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Madrenas","sequence":"additional","affiliation":[{"name":"Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University , Montreal, Quebec H3A 2B4,","place":["Canada"]},{"name":"Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center , Torrance, CA 90277"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,2,15]]},"reference":[{"key":"2025030610015093800_r1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"Lowy","year":"1998","journal-title":"N. 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