{"id":2057,"date":"2026-05-21T10:00:00","date_gmt":"2026-05-21T10:00:00","guid":{"rendered":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/05\/21\/immunology-time-the-target-in-ms\/"},"modified":"2026-05-21T10:00:00","modified_gmt":"2026-05-21T10:00:00","slug":"immunology-time-the-target-in-ms","status":"publish","type":"post","link":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/05\/21\/immunology-time-the-target-in-ms\/","title":{"rendered":"Immunology Time..The Target in MS"},"content":{"rendered":"
Tweet<\/a><\/div>\n

Many years ago the new target for MS was reported and it was called RASGRP2. People then wanted to inhibit responses to this protein to treat MS…I thought the idea was a crock and I said this to one of the leading authors of the original discovery at a meeting in Sweden….I asked how can this be the target for MS, when the target (RASGRP2) is not really expressed in the CNS on the presumed target for MS, which is the oligodendrocyte?…..There was silence from the speaker in response to the question. There was a gasp and horror in the crowd. How dare I question the great and the good about their Naturey\/Sciencey<\/em> work? <\/p>\n

However they had been telling us for years that the problem was response to myelin basic protein<\/p>\n

They said that the molecule was expressed on nerves and showed a picture of wishy-washy staining, not really making any comment of the fact that picture showed that the the stuff within the blood vessel was lighting up like a christmas tree. This could mean there was non-specific staining or the cellular target was really a blood protein. Well this is evident because RASGRP2 is a protein on platelets, which are involved in blood clotting and also the immune cells such as B cells. Why MS, when the target is found all over the place?<\/p>\n

\"\"<\/figure>\n
\"\"<\/figure>\n

Source Protein Atlas.org https:\/\/www.proteinatlas.org\/ENSG00000068831-RASGRP2\/single+cell<\/a><\/p>\n

If it is on nerves maybe following destruction of nerves you get an immune response to it as a secondary event. In this study they do alot of work and find a bit of the protein that people with an MS-assocoiated gene respond to and find that responses to this are more common in MS than controls. They come up with a different peptide to that originally was reported to be interesting. This could be an epiphenomenon and they way you prove it to be interesting is to remove the immune response to the target and disease should go away….This is not a simple task and as you dont know for sure this is the causative target, it is risky to develop this in MS. So whilst antigen-specific immunotherapy is a holy grail of therapy as it should get rid of disease without side-effects…well that’s the logic, proof is in the pudding. <\/p>\n

Li V, Pandey K, Binder MD, Reid HH, Lim JJ, Loh TJ, Tran MT, Rossjohn J, Purcell AW, Kilpatrick TJ. Identification of an immunogenic epitope from with specificity for HLA-DR15 in multiple sclerosis. J Neuroimmunol. 2026 May 15;418:578971.<\/p>\n

Identifying autoantigens in multiple sclerosis (MS) has been challenging. If successful, this could facilitate development of autoantigen-specific tolerogenic therapies, by exposing antigen presenting cells (APC) to tolerogenic stimuli with autoantigens specific to the human leukocyte antigen (HLA) haplotype of patients. RAS guanyl releasing protein 2 (RASGRP2), which is expressed by lymphocytes and striatal neurons, is a putative autoantigen in HLA-DRB1*15:01 (DR15)-positive individuals<\/strong>. We aimed to identify antigenic RASGRP2 epitope(s) that could be used to develop tolerogenic therapies. RASGRP2-derived peptides of varying DR15 binding affinities were exposed to peripheral blood mononuclear cells (PBMCs).<\/strong> Immunoeptidomic techniques demonstrated strong and moderate binding affinity RASGRP2 peptides could be presented by HLA-DR on PBMCs from DR15-homozygous or DR15-negative patients. Moderate affinity peptides <\/strong>produced the greatest increase in CD80 expression and pro-inflammatory cytokine (IFN-\u03b3, IL-17, IL-22) secretion by PBMCs, particularly in DR15-positive patients. One RASGRP2 peptide eliciting the highest pro-inflammatory responses was used to generate HLA-DR15 tetramers. <\/strong>CD4+ T-cells specific for this peptide were four-fold higher in frequency in DR15-positive patients versus controls, more pro-inflammatory in phenotype and demonstrated increased peptide-stimulated proliferation. In conclusion, we identified a novel immunogenic RASGRP2 peptide with relative selectivity for HLA-DR15-positive people with MS, which could form the basis for autoantigen-specific tolerogenic therapy.<\/em><\/p>\n

Source: multiple-sclerosis-research.org<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Tweet Many years ago the new target for MS was reported and it was called RASGRP2. People then wanted to inhibit responses to this protein to treat MS…I thought the idea was a crock and I said this to one of the leading authors of…<\/p>\n","protected":false},"author":0,"featured_media":2058,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[11,15,9,8,13,14,12,10],"class_list":["post-2057","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-multiple-sclerosis-research","tag-brain-repair","tag-marburg-type-ms","tag-ms","tag-multiple-sclerosis","tag-myelin","tag-neuroregeneration","tag-oligodendrocyte","tag-remyelination"],"_links":{"self":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/2057","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/comments?post=2057"}],"version-history":[{"count":0,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/2057\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/media\/2058"}],"wp:attachment":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/media?parent=2057"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/categories?post=2057"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/tags?post=2057"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}