Peptide mimics of a tumor antigen induce functional cytotoxic T cells

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.