{"id":63982,"date":"2026-05-12T19:18:12","date_gmt":"2026-05-12T17:18:12","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/05\/12\/the-subset-of-m1-paired-mhc-class-ii-conformers-is-critical-for-cd4-t-cell-activation\/"},"modified":"2026-05-12T19:18:12","modified_gmt":"2026-05-12T17:18:12","slug":"the-subset-of-m1-paired-mhc-class-ii-conformers-is-critical-for-cd4-t-cell-activation","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/05\/12\/the-subset-of-m1-paired-mhc-class-ii-conformers-is-critical-for-cd4-t-cell-activation\/","title":{"rendered":"The subset of M1-paired MHC class II conformers is critical for CD4+ T cell activation"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Apr 15;215(4):vkag093. doi: 10.1093\/jimmun\/vkag093.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<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-conformer 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 &gt;90% of T cell activation by ovalbumin peptide-I-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-restricted T cell-dependent 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-dependent 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.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42118109\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260512131812&amp;v=2.20.0\">42118109<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag093\">10.1093\/jimmun\/vkag093<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Apr 15;215(4):vkag093. doi: 10.1093\/jimmun\/vkag093. ABSTRACT 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. &#8230; <a title=\"The subset of M1-paired MHC class II conformers is critical for CD4+ T cell activation\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/05\/12\/the-subset-of-m1-paired-mhc-class-ii-conformers-is-critical-for-cd4-t-cell-activation\/\" aria-label=\"Read more about The subset of M1-paired MHC class II conformers is critical for CD4+ T cell activation\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-63982","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/63982","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=63982"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/63982\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=63982"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=63982"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=63982"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}