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Autoimmune disease – retraining white blood cells.



Engineering antigens for in situ erythrocyte binding induces T-cell deletion.

"Antigens derived from apoptotic cell debris can drive clonal T-cell deletion or anergy, and antigens chemically coupled ex vivo to apoptotic cell surfaces have been shown correspondingly to induce tolerance on infusion. Reasoning that a large number of erythrocytes become apoptotic (eryptotic) and are cleared each day, the group of Prof. Jeffrey Alan Hubbell (Merck Serono Chair in Drug Delivery) engineered two different antigen constructs to target the antigen to erythrocyte cell surfaces after i.v. injection, one using a conjugate with an erythrocyte-binding peptide and another using a fusion with an antibody fragment, both targeting the erythrocyte-specific cell surface marker glycophorin A. They report a translatable modular biomolecular approach with which to engineer antigens for targeted binding to erythrocyte cell surfaces to induce antigen-specific CD4+ and CD8+ T-cell deletion toward exogenous antigens and autoantigens."

See: Stephan Kontos, Iraklis C. Kourtis, Karen Y. Dane, and Jeffrey A. Hubbell, PNAS doi: 10.1073/pnas.1216353110 (2012)