{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:28:34Z","timestamp":1762928914439,"version":"build-2065373602"},"reference-count":212,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["Project No. 007491"],"award-info":[{"award-number":["Project No. 007491"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["Project UIDB\/00709\/2020"],"award-info":[{"award-number":["Project UIDB\/00709\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Studies carried out during the last few decades have consistently shown that cell surface MHC class I (MHC-I) molecules are endowed with functions unrelated with antigen presentation. These include cis\u2013trans-interactions with inhibitory and activating KIR and LILR, and cis-interactions with receptors for hormones, growth factors, cytokines, and neurotransmitters. The mounting body of evidence indicates that these non-immunological MHC-I functions impact clinical and biomedical settings, including autoimmune responses, tumor escape, transplantation, and neuronal development. Notably, most of these functions appear to rely on the presence in hematopoietic and non-hematopoietic cells of heavy chains not associated with \u03b22m and the peptide at the plasma membrane; these are known as open MHC-I conformers. Nowadays, open conformers are viewed as functional cis-trans structures capable of establishing physical associations with themselves, with other surface receptors, and being shed into the extracellular milieu. We review past and recent developments, strengthening the view that open conformers are multifunctional structures capable of fine-tuning cell signaling, growth, differentiation, and cell communication.<\/jats:p>","DOI":"10.3390\/ijms22189738","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T21:28:45Z","timestamp":1631136525000},"page":"9738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Open MHC Class I Conformers: A Look through the Looking Glass"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7209-4507","authenticated-orcid":false,"given":"Fernando A.","family":"Arosa","sequence":"first","affiliation":[{"name":"Health Sciences Research Center (CICS-UBI), University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-4337","authenticated-orcid":false,"given":"Andr\u00e9 J.","family":"Esgalhado","sequence":"additional","affiliation":[{"name":"Health Sciences Research Center (CICS-UBI), University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8769-1355","authenticated-orcid":false,"given":"D\u00e9bora","family":"Reste-Ferreira","sequence":"additional","affiliation":[{"name":"Health Sciences Research Center (CICS-UBI), University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6937-6474","authenticated-orcid":false,"given":"Elsa M.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Health Sciences Research Center (CICS-UBI), University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"Health School, Guarda Polytechnic Institute, 6300-749 Guarda, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"ref_1","unstructured":"Klein, J. 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