{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:51:11Z","timestamp":1787021471036,"version":"build-2736575974"},"reference-count":61,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T00:00:00Z","timestamp":1458172800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Major histocompatibility complex (MHC) class II molecules present exogenously derived antigen peptides to CD4 T cells, driving activation of na\u00efve T cells and supporting CD4-driven immune functions. However, MHC class II molecules are not inert protein pedestals that simply bind and present peptides. These molecules also serve as multi-functional signaling molecules delivering activation, differentiation, or death signals (or a combination of these) to B cells, macrophages, as well as MHC class II-expressing T cells and tumor cells. Although multiple proteins are known to associate with MHC class II, interaction with STING (stimulator of interferon genes) and CD79 is essential for signaling. In addition, alternative transmembrane domain pairing between class II \u03b1 and \u03b2 chains influences association with membrane lipid sub-domains, impacting both signaling and antigen presentation. In contrast to the membrane-distal region of the class II molecule responsible for peptide binding and T-cell receptor engagement, the membrane-proximal region (composed of the connecting peptide, transmembrane domain, and cytoplasmic tail) mediates these \u201cnon-traditional\u201d class II functions. Here, we review the literature on the function of the membrane-proximal region of the MHC class II molecule and discuss the impact of this aspect of class II immunobiology on immune regulation and human disease.<\/ns4:p>","DOI":"10.12688\/f1000research.7610.1","type":"journal-article","created":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T13:16:13Z","timestamp":1458220573000},"page":"368","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Immunological Functions of the Membrane Proximal Region of MHC Class II Molecules"],"prefix":"10.12688","volume":"5","author":[{"given":"Jonathan","family":"Harton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7675-6443","authenticated-orcid":false,"given":"James","family":"Drake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2016,3,17]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"27101-27112","DOI":"10.1074\/jbc.M115.649582","article-title":"Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules.","volume":"290","author":"M 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