{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHLA‐DRB3, a lesser expressed class II gene that partners with several HLA‐DRB1 alleles to form conserved haplotypes, modulates antigen presentation and T‐cell recognition in multiple immune-mediated conditions. Its expression and allele variation have been shown to influence disease phenotypes such as sarcoidosis, where specific DRB3 alleles may be markers for bone marrow involvement, and in allogeneic hematopoietic stem cell transplantation, where mismatches involving DRB3 (along with DRB4/5) can impact graft‐versus‐host outcomes. In autoimmune hepatitis, DRB3*0101 in combination with disease‐associated DRB1 molecules has been identified as part of the genetic risk profile."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, allele‐specific effects of HLA‐DRB3 have been implicated in the modulation of autoimmunity and infection. In type 1 diabetes, for example, the presence of DRB3*02:02 on a DRB1*03:01 haplotype has been shown to modify risk and associate with distinct autoantibody profiles, emphasizing its role in fine‐tuning immunogenetic susceptibility. Similarly, DRB3 alleles have been linked to enhanced clearance of hepatitis C virus in Caucasians, further highlighting their influence on shaping the antiviral CD4 T‐cell response. Detailed analyses of extended MHC haplotypes have reinforced that DRB3, although not always the primary susceptibility determinant, can contribute to disease risk within the context of DRB1-associated haplotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, structural and functional studies elucidate how HLA‐DRB3 molecules, such as DR52a encoded by DRB3*0101, present distinct peptide repertoires and govern the immune response in conditions like neonatal alloimmune thrombocytopenia, where DRB3*0101 restricts HPA‐1a‐specific T cells. This structural insight into peptide binding pockets provides a mechanistic basis for allele‐specific immune responses observed in diverse autoimmune and alloimmune settings"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Milton D Rossman, Bruce Thompson, Margaret Frederick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/378097"}], "href": "https://doi.org/10.1086/378097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14508706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14508706"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marcelo A Fernández-Viña, John P Klein, Michael Haagenson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple mismatches at the low expression HLA loci DP, DQ, and DRB3/4/5 associate with adverse outcomes in hematopoietic stem cell transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2013-02-481945"}], "href": "https://doi.org/10.1182/blood-2013-02-481945"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23596045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23596045"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lea Campos Oliveira, Gilda Porta, Maria Lucia C Marin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autoimmune hepatitis, HLA and extended haplotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autoimmun Rev (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.autrev.2010.09.024"}], "href": "https://doi.org/10.1016/j.autrev.2010.09.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20933106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20933106"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "K Bogunia-Kubik, J Tomeczko, K Suchnicki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HLA-DRB1"}, {"type": "i", "children": [{"type": "t", "text": "03, DRB1*11 or DRB1"}]}, {"type": "t", "text": "12 and their respective DRB3 specificities in clinical variants of sarcoidosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Antigens (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1034/j.1399-0039.2001.057001087.x"}], "href": "https://doi.org/10.1034/j.1399-0039.2001.057001087.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11169267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11169267"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "A Rojana-udomsart, M Needham, Y B Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The association of sporadic inclusion body myositis and Sjögren's syndrome in carriers of HLA-DR3 and the 8.1 MHC ancestral haplotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Neurol Neurosurg (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clineuro.2011.03.016"}], "href": "https://doi.org/10.1016/j.clineuro.2011.03.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21507567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21507567"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rebecca A Harris, Kazushi Sugimoto, David E Kaplan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specific CD4 T cell response among Caucasians and African Americans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.22287"}], "href": "https://doi.org/10.1002/hep.22287"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18537178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18537178"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Henry A Erlich, Ana Maria Valdes, Shana L McDevitt, et al. 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