Peptide mimics of a tumor antigen induce functional cytotoxic T cells

Nat Biotechnol. 1998 Mar;16(3):276-80. doi: 10.1038/nbt0398-276.

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Epitopes
  • Female
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • Humans
  • Immunization
  • Immunotherapy / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred Strains
  • Models, Molecular
  • Molecular Sequence Data
  • Mucin-1
  • Mucins
  • Mutation
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Neoplasms, Experimental / immunology
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / immunology*
  • Protein Conformation
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Epitopes
  • HLA-A Antigens
  • MUC1 protein, human
  • Mucin-1
  • Mucins
  • Peptides