Peptide mimics of a tumor antigen induce functional cytotoxic T cells

Nature Biotechnology
Vasso ApostolopoulosI F McKenzie

Abstract

The ability to mimic peptide/peptide and/or peptide/carbohydrate structures may be important in generating cross-reactive antibodies for autoimmune and other diseases. We show that the peptide sequence DAHWESWL can mimic the conformation of the unrelated MUC1 peptide SAPDTRPAP(G). Mice immunized with mannan-MUC1-peptides make cytotoxic T lymphocytes (CTLs) and are protected from MUC1+ tumors. We show that the same specific anti-MUC1 responses can be produced by immunizing with the DAHWESWL peptide; furthermore, specific tumor protection is obtained in a manner similar to that with MUC1 immunization. The DAHWESWL peptide immunization leads to CTLs that recognize H2Dd and H2Ld but not H2b or human leukocyte antigens-group A (HLA-A) *0201 presented MUC1 peptides. However, mutation of the DAHWESWL peptide to a more HLA-A*0201-compatible structure with appropriate anchors (DLHWASWV), leads to the production of CTLs in HLA-A*0201 mice.

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Citations

Jun 5, 2003·International Journal for Parasitology·Gina Cunto-AmestyThomas Kieber-Emmons
Oct 3, 1999·Vaccine·V ApostolopoulosI F McKenzie
Jan 22, 2003·Immunology and Cell Biology·Ian F C McKenzieBruce E Loveland
Jul 11, 2006·Immunology·Kuo-Ching ShengVasso Apostolopoulos
Nov 15, 2013·Journal of Drug Delivery·Vasso ApostolopoulosLily Stojanovska
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Sep 5, 2008·Expert Review of Vaccines·Choon-Kit TangVasso Apostolopoulos
Sep 5, 2008·Expert Review of Vaccines·Choon-Kit TangGeoffrey A Pietersz
Jan 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jim J C SheuTse-Wen Chang
Jun 4, 2010·Expert Review of Vaccines·Magdalena PlebanskiVasso Apostolopoulos
May 15, 2020·Brain Sciences·Vasso ApostolopoulosJohn Matsoukas
Dec 1, 2020·Expert Review of Vaccines·Md Kamal HossainVasso Apostolopoulos
May 7, 2020·ACS Infectious Diseases·Edward Valencia AyalaAlexandre F Marques
Jan 19, 2007·Molecular Pharmaceutics·Owen ProudfootGeoffrey A Pietersz

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