Peptide mimics of a tumor antigen induce functional cytotoxic T cells.
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.
Apostolopoulos
V
V
Austin Research Institute, Heidelberg, Victoria, Australia.
Lofthouse
S A
SA
Popovski
V
V
Chelvanayagam
G
G
Sandrin
M S
MS
McKenzie
I F
IF
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000939:Epitopes; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins; D009154:Mutation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000276:immunology; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000939:Epitopes; D015234:HLA-A Antigens; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D010455:Peptides