{"id":1134,"date":"2020-05-29T16:20:31","date_gmt":"2020-05-29T08:50:31","guid":{"rendered":"http:\/\/bioactivecompoundlibrary.com\/?p=1134"},"modified":"2022-01-11T17:18:21","modified_gmt":"2022-01-11T09:48:21","slug":"hla-g-dimers-reported-trophoblast-cells-confers-protection-immune-system","status":"publish","type":"post","link":"http:\/\/bioactivecompoundlibrary.com\/index.php\/2020\/05\/29\/hla-g-dimers-reported-trophoblast-cells-confers-protection-immune-system\/","title":{"rendered":"HLA-G dimers has been reported in trophoblast cells where it confers protection against the immune system"},"content":{"rendered":"

This mechanism of natural tolerance in a semiallogeneic context has led to investigate the potential role of HLAG in transplanted patients. To date, clinical studies have demonstrated that HLA-G expression may be induced in some heart, kidney, liver\/kidney, lung, pancreas, and kidney\/pancreas transplanted patients. Statistical analyses indicate that the presence of HLA-G in plasma and biopsies of transplanted patients correlates with a decreased number of acute rejection episodes and with no chronic rejection, as first described for heart transplants. The direct role of HLA-G in transplantation in vivo was evidenced by skin allotransplantation in HLA-G transgenic mice or in wild-type mice pre-treated with HLA-G tetramer-coated beads. In both experiments the presence of HLA-G significantly delayed skin allograft rejection. For these reasons, and also because it already contributes to the best example of successful tolerance there is: the maternal-fetal tolerance, therapeutic HLA-G molecules for transplantation are actively investigated. Yet, the use of HLA-G molecules as therapeutic agents faces several hurdles, among which the problems of structure and stability. Indeed, HLA-G is a trimolecular complex composed of a heavy chain of 3 globular domains non-covalently associated with the b2-microglobulin and a peptide which is active only as a multimer. Here, we evaluated the tolerogenic function of two types of HLA-G homodimers, whether the alpha-1 domain of HLA-G which is common to all HLA-G isoforms could carry a tolerogenic function by itself as it was originally postulated, and whether the trimolecular complex that constitutes HLA-G could be stabilized by fusing B2M to HLA-G heavy chain while retaining its tolerogenic properties. Our results demonstrate the tolerogenic function of all investigated dimeric forms of HLA-G recombinant proteins in vitro and in vivo, and especially that of the B2M-HLA-G5 dimers in vivo, but do not fully support a tolerogenic function for the alpha-1 domain of HLA-G in human beings, even dimeric. In this work, we investigated the tolerogenic properties of HLAG recombinant proteins. These were B2M-HLA-G heavy chain fusions and HLA-G alpha-1 domains dimerized either through an Fc fragment, or naturally through a C42-C42 disulfide bond. Of note, because of the presence of B2M and the linker in our constructs, the cysteines involved in HLA-G homodimerization were no Paclitaxel<\/a> longer in position 42, but for the sake of clarity, we kept calling C42 the cysteines of the HLA-G alpha-1 domain that are responsible for homodimerization. Our first aim was to evaluate the tolerogenic function of two types of single-chain B2M-HLA-G homodimers. In this study, we showed that all generated proteins and peptide were multimerized. Furthermore, B2M-HLA-G fusions were properly folded and could bind and activate the ILT2 receptor.<\/p>\n","protected":false},"excerpt":{"rendered":"

This mechanism of natural tolerance in a semiallogeneic context has led to investigate the potential role of HLAG in transplanted patients. To date, clinical studies have demonstrated that HLA-G expression may be induced in some heart, kidney, liver\/kidney, lung, pancreas, and kidney\/pancreas transplanted patients. Statistical analyses indicate that the presence of HLA-G in plasma and… Continue reading HLA-G dimers has been reported in trophoblast cells where it confers protection against the immune system<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1134"}],"collection":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/comments?post=1134"}],"version-history":[{"count":1,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1134\/revisions"}],"predecessor-version":[{"id":1135,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1134\/revisions\/1135"}],"wp:attachment":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/media?parent=1134"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/categories?post=1134"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/tags?post=1134"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}