{"id":36385,"date":"2025-06-27T12:49:47","date_gmt":"2025-06-27T10:49:47","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/06\/27\/lag3-mhcii-interaction-induces-a-tight-cell-cell-interface-at-the-immunological-synapse\/"},"modified":"2025-06-27T12:49:47","modified_gmt":"2025-06-27T10:49:47","slug":"lag3-mhcii-interaction-induces-a-tight-cell-cell-interface-at-the-immunological-synapse","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/06\/27\/lag3-mhcii-interaction-induces-a-tight-cell-cell-interface-at-the-immunological-synapse\/","title":{"rendered":"LAG3-MHCII interaction induces a tight cell-cell interface at the immunological synapse"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Jun 26:vkaf120. doi: 10.1093\/jimmun\/vkaf120. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Lymphocyte activation gene 3 (LAG3), an immune checkpoint, inhibits T cell function by binding to major histocompatibility complex class II (MHCII). Although LAG3 holds significant therapeutic potential for cancer immunotherapy, the molecular mechanisms underlying LAG3-mediated immunosuppression remain poorly characterized. Here, using a reconstituted cell conjugation assay, we demonstrate that LAG3 binds directly to MHCII in a T cell receptor signaling-independent manner. Beyond its role in modulating intercellular adhesion, the LAG3-MHCII interaction remodels the architecture of the immunological synapse (IS). Correlative light and electron microscopy reveals that the LAG3-MHCII interaction creates a remarkably tight cell-cell interface at the IS, which selectively excludes CD4, large receptor-ligand complexes, and whole IgG of LAG3 antibodies. Conversely, the Fab fragment of LAG3 antibodies can penetrate this tight interface, block LAG3-MHCII binding, and enhance T cell responses. In addition, the LAG3-MHCII interaction directly facilitates MHCII trogocytosis. These findings demonstrate that the LAG3-MHCII interaction establishes a selective physical barrier at the IS, providing novel mechanistic insights into LAG3-mediated immunosuppression and suggesting feasible strategies for the development of more effective immunotherapeutic drugs.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40574316\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250627064946&amp;v=2.18.0.post9+e462414\">40574316<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf120\">10.1093\/jimmun\/vkaf120<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Jun 26:vkaf120. doi: 10.1093\/jimmun\/vkaf120. Online ahead of print. ABSTRACT Lymphocyte activation gene 3 (LAG3), an immune checkpoint, inhibits T cell function by binding to major histocompatibility complex class II (MHCII). Although LAG3 holds significant therapeutic potential for cancer immunotherapy, the molecular mechanisms underlying LAG3-mediated immunosuppression remain poorly characterized. Here, using a reconstituted &#8230; <a title=\"LAG3-MHCII interaction induces a tight cell-cell interface at the immunological synapse\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/06\/27\/lag3-mhcii-interaction-induces-a-tight-cell-cell-interface-at-the-immunological-synapse\/\" aria-label=\"Read more about LAG3-MHCII interaction induces a tight cell-cell interface at the immunological synapse\">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-36385","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\/36385","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=36385"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36385\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=36385"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=36385"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=36385"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}