{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:09:00Z","timestamp":1788786540797,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":41,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Albany Medical College Institutional Funds"},{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["R03AI165365"],"award-info":[{"award-number":["R03AI165365"]}]},{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["R01AI148354"],"award-info":[{"award-number":["R01AI148354"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Major histocompatibility complex class II molecules present exogenous antigen-derived peptide to CD4+ T cells leading to T cell activation as well as signaling into the antigen-presenting cell. Class II is an \u03b1\u03b2 heterodimer that forms 2 distinct conformers via differential pairing of transmembrane domain GxxxG motifs (i.e. M1- and M2-paired class II). Previous studies with mouse I-Ak and human HLA-DR class II used conformer-specific monoclonal antibodies (mAbs) to define unique immunobiological properties of each conformer. Here, we report that AMS-32.1, a widely used anti-I-Ad mAb, is-specific for the 20% of M1-paired I-Ad class II expressed by the cell, and 34-5-3S anti-I-Ad mAb is non\u2013conformer specific. While AMS-32.1 engagement of M1-paired I-Ad elicits B cell calcium signaling, 34-5-3S coengagement of M1 and M2-paired I-Ad blocks this response, indicating M2-paired class II inhibits M1-paired class II signaling. In vitro, AMS-32.1 blocks &amp;gt;90% of T cell activation by ovalbumin peptide\u2013I-Ad complexes, even under conditions where peptide is loaded onto both conformers. In vivo, AMS-32.1 blocks accumulation of ovalbumin-specific CD4+ T cells in the spleen and lymph nodes. In a murine model of hepatitis B virus replication, in which major histocompatibility complex class II\u2013restricted T cell\u2013dependent humoral responses are key to antigen clearance, AMS-32.1 blocks hepatitis B surface antigen seroconversion, indicating that M1-paired class II is central to the in vivo development of CD4+ T cell\u2013dependent antibody responses. Overall, this study reveals that AMS-32.1 is specific for M1-paired I-Ad class II and that M1-paired class II is critical for CD4+ T cell activation both in vitro and in vivo.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag093","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T14:34:24Z","timestamp":1778596464000},"source":"Crossref","is-referenced-by-count":1,"title":["The subset of M1-paired MHC class II conformers is critical for CD4+ T cell activation"],"prefix":"10.1093","volume":"215","author":[{"given":"Sophia","family":"Cangialosi","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College , Albany, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse L","family":"Cimino","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College , Albany, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safiehkhatoon","family":"Moshkani","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College , Albany, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Kryzak","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College , Albany, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Robek","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College , Albany, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Drake","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Disease, Albany Medical College , Albany, 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