Blood leukocytes recapitulate diabetogenic peptide–MHC-II complexes displayed in the pancreatic islets

Anthony N. Vomund, Cheryl F. Lichti, Orion J. Peterson, Ana Maria Arbelaez, Xiaoxiao Wan, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Assessing the self-peptides presented by susceptible major histocompatibility complex (MHC) molecules is crucial for evaluating the pathogenesis and therapeutics of tissue-specific autoimmune diseases. However, direct examination of such MHC-bound peptides displayed in the target organ remains largely impractical. Here, we demonstrate that the blood leukocytes from the nonobese diabetic (NOD) mice presented peptide epitopes to autoreactive CD4 T cells. These peptides were bound to the autoimmune class II MHC molecule (MHC-II) I-Ag7 and originated from insulin B-chain and C-peptide. The presentation required a glucose challenge, which stimulated the release of the insulin peptides from the pancreatic islets. The circulating leukocytes, especially the B cells, promptly captured and presented these peptides. Mass spectrometry analysis of the leukocyte MHC-II peptidome revealed a series of β cell–derived peptides, with identical sequences to those previously identified in the islet MHC-II peptidome. Thus, the blood leukocyte peptidome echoes that found in islets and serves to identify immunogenic peptides in an otherwise inaccessible tissue.

Original languageEnglish
Article numbere20202530
JournalJournal of Experimental Medicine
Volume218
Issue number6
DOIs
StatePublished - Apr 6 2021

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