{"id":76729,"date":"2026-09-18T00:43:47","date_gmt":"2026-09-17T22:43:47","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/09\/18\/immunopeptidomics-driven-mhc-class-ii-peptide-binding-motif-discovery-for-2-common-canine-dr-alleles\/"},"modified":"2026-09-18T00:43:47","modified_gmt":"2026-09-17T22:43:47","slug":"immunopeptidomics-driven-mhc-class-ii-peptide-binding-motif-discovery-for-2-common-canine-dr-alleles","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/09\/18\/immunopeptidomics-driven-mhc-class-ii-peptide-binding-motif-discovery-for-2-common-canine-dr-alleles\/","title":{"rendered":"Immunopeptidomics-driven MHC class II peptide-binding motif discovery for 2 common canine DR alleles"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Aug 29;215(9):vkag243. doi: 10.1093\/jimmun\/vkag243.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Despite the central role of major histocompatibility complex (MHC) class II in adaptive immunity, peptide-binding motifs have yet to be characterized for any canine MHC class II allele. Here, we report the first immunopeptidomics-derived binding motifs for DLA-DRB1*015:01 (DLA-DR15) and DLA-DRB1*012:01 (DLA-DR12), 2 alleles overrepresented in breeds predisposed to immune-mediated diseases. Because dogs co-express DLA-DR and DLA-DQ, the MHC class II Ab clone YKIX334.2 was validated to be DLA-DR-specific, enabling allele-selective immunoaffinity purification of DLA-DR molecules from homozygous DLA-DR15 and DLA-DR12 donor spleens. Mass spectrometry and GibbsCluster motif deconvolution of 838 DLA-DR15-associated and 644 DLA-DR12-associated peptides eluted from their respective peptide-binding grooves revealed distinct allele-specific binding motifs, with characterization of anchor residue preferences, peptide-length distributions, cross-species comparisons with human and murine MHC class II motifs, and source protein composition of the eluted self-peptidome. To evaluate the translational utility of these motifs, recombinant DLA-DR15 and DLA-DR12 molecules were used to screen rabies virus glycoprotein and nucleoprotein peptide libraries via fluorescence-based peptide competition assays, identifying high-affinity candidate binders for both alleles. Spearman rank correlation between immunopeptidomics-derived position-specific scoring matrix scores and peptide competition assay rankings demonstrated modest associations, consistent with these approaches capturing complementary dimensions of peptide-MHC class II interaction. Ultimately, these findings establish what we believe is the first allele-specific peptide-binding motif framework for canine MHC class II, providing a foundation for DLA-allele-informed CD4+ T-cell epitope discovery studies and Ag-specific immune response characterization in the dog.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42752862\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260917184346&amp;v=2.20.1\">42752862<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag243\">10.1093\/jimmun\/vkag243<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Aug 29;215(9):vkag243. doi: 10.1093\/jimmun\/vkag243. ABSTRACT Despite the central role of major histocompatibility complex (MHC) class II in adaptive immunity, peptide-binding motifs have yet to be characterized for any canine MHC class II allele. Here, we report the first immunopeptidomics-derived binding motifs for DLA-DRB1*015:01 (DLA-DR15) and DLA-DRB1*012:01 (DLA-DR12), 2 alleles overrepresented in breeds &#8230; <a title=\"Immunopeptidomics-driven MHC class II peptide-binding motif discovery for 2 common canine DR alleles\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/09\/18\/immunopeptidomics-driven-mhc-class-ii-peptide-binding-motif-discovery-for-2-common-canine-dr-alleles\/\" aria-label=\"Read more about Immunopeptidomics-driven MHC class II peptide-binding motif discovery for 2 common canine DR alleles\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-76729","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\/76729","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=76729"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/76729\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=76729"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=76729"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=76729"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}