{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:08:33Z","timestamp":1788800913006,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK063158"],"award-info":[{"award-number":["R01 DK063158"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Post\u2010translational modifications (PTMs) can generate neo\u2010epitopes, modified peptides that evade immune tolerance and trigger immune responses. This review focuses on the TG2\/LRP1 pathway as a new paradigm for coupling the formation of post\u2010translationally modified peptides with their effective presentation as T\u2010cell antigens by dendritic cells. Transglutaminase 2 (TG2) catalyzes the Gln\u2009\u2192\u2009Glu conversion of specific residues in peptides derived from dietary gluten thereby enhancing their affinity for HLA\u2010DQ2, the principal genetic determinant of celiac disease. However, because such modified peptides are scarce in intestinal mucosa, an effective mechanism for lysosomal uptake by antigen\u2010presenting cells (APCs) is necessary. Protein\u2013protein interaction between certain peptide\u2010bound TG2 complexes and the low\u2010density lipoprotein receptor\u2010related protein 1 (LRP1) results in efficient endocytosis of these antigenic peptides along with their concomitant release in the endo\u2010lysosomal compartment as deamidated products. An analogous PTM\u2010driven mechanism for antigen presentation may also operate in autoimmune conditions associated with peptidylarginine deiminase (PADI) activity, such as rheumatoid arthritis (RA). The exquisite cellular selectivity of the TG2\/LRP1 pathway has implications not only for understanding its role in autoimmunity but also for its potential exploitation in vaccine design.<\/jats:p>","DOI":"10.1111\/imr.70155","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:19:10Z","timestamp":1785903550000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>TG2<\/scp>\n                    \/\n                    <scp>LRP1<\/scp>\n                    Pathway for T Cell Activation by Post\u2010Translationally Modified Antigens"],"prefix":"10.1111","volume":"341","author":[{"given":"Agnele Sylvia","family":"Sewa","sequence":"first","affiliation":[{"name":"Department of Biochemistry Stanford University School of Medicine  Stanford California 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