{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Alpha1,3‐galactosyltransferase 2 (A3GALT2), also known as iGb3 synthase, is a glycosyltransferase that catalyzes the transfer of galactose in an α1,3‐linkage to form isoglobotrihexosylceramide (iGb3), a glycosphingolipid with a terminal α‐galactose moiety. Although early studies proposed that iGb3 might serve as an endogenous ligand for CD1d and thereby play a critical role in invariant natural killer T (iNKT) cell development and self‐recognition, genetic ablation of A3GALT2 in mice did not alter iNKT cell numbers or T‐cell receptor repertoire, demonstrating that iGb3 is not essential for thymic iNKT cell selection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Furthermore, in humans the A3GALT2 gene appears to be nonfunctional, precluding the synthesis of iGb3 and further underscoring species‐specific differences in glycosphingolipid metabolism and antigen presentation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " As a member of the GT6 gene family, A3GALT2 contributes to the diversification of terminal glycosphingolipid structures, and its activity influences the repertoire of glycolipid antigens that can be recognized by natural antibodies and, potentially, by immune effector cells. In the context of xenotransplantation, residual α‐galactosyl epitopes, which may arise in part via A3GALT2‐mediated pathways, have been scrutinized for their role in eliciting antibody‐mediated rejection; however, studies employing double‐knockout strategies in donor pigs indicate that while A3GALT2 deletion alters the glycosphingolipid profile, its elimination does not significantly modify the overall binding of human or primate antibodies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, comparative structural analyses of paralogous glycosyltransferases, including A3GALT2, highlight how subtle variations in the substrate‐binding domains underlie diverse sugar specificities and tissue expression patterns that ultimately modulate immune recognition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stefan Porubsky, Anneliese O Speak, Bruno Luckow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0611139104"}], "href": "https://doi.org/10.1073/pnas.0611139104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17372206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17372206"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dale Christiansen, Julie Milland, Effie Mouhtouris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Humans lack iGb3 due to the absence of functional iGb3-synthase: implications for NKT cell development and transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.0060172"}], "href": "https://doi.org/10.1371/journal.pbio.0060172"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18630988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18630988"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "James R Butler, Nicholas J Skill, David L Priestman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing the porcine iGb3s gene does not affect Galα3Gal levels or measures of anticipated pig-to-human and pig-to-primate acute rejection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Xenotransplantation (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/xen.12217"}], "href": "https://doi.org/10.1111/xen.12217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27106872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27106872"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Emili Cid, Miyako Yamamoto, Fumiichiro Yamamoto "}, {"type": "b", "children": [{"type": "t", "text": "Amino acid substitutions at sugar-recognizing codons confer ABO blood group system-related α1,3 Gal(NAc) transferases with differential enzymatic activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-37515-5"}], "href": "https://doi.org/10.1038/s41598-018-37515-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30696937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30696937"}]}]}]}