Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1.
The epithelial mucin MUC1 is one of the few tumour-associated antigens identified for breast cancer. Several MUC1-derived peptides binding HLA-A*0201 molecules have been identified that correspond to sequences outside the tandem repeat. Immunisation with some of these peptides induces protective antitumour immunity in mice. Another HLA-A*0201-binding peptide has been identified in a human system. We have evaluated the CD8(+) T-cell responses to all these peptides using peripheral blood lymphocytes from breast cancer patients and normal donors. Specific CD8(+) T-cell responses could be generated in vitro against some of these peptides but only after several rounds of in vitro restimulation, and they did not recognise human cells endogenously expressing the antigen. Nevertheless, T cells recognised by HLA-A*0201 tetramers carrying a peptide from the signal sequence (LLLLTVLTV) could be detected in the peripheral blood of some HLA-A*0201(+) breast cancer patients but not in healthy adults. This peptide is the only one of those tested which was identified in the human system, and the results emphasize the potential problems involved in translation of data from laboratory animal models to the human system.
Correa
Isabel
I
Breast Cancer Biology Group, Cancer Research UK, Guy's Hospital, London, United Kingdom.
Plunkett
Timothy
T
Coleman
Julia
J
Galani
Eleni
E
Windmill
Elisabeth
E
Burchell
Joy M
JM
Taylor-Papdimitriou
Joyce
J
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D008214:Lymphocytes; D051379:Mice; D018396:Mucin-1 / Q000235:genetics* / Q000276:immunology*; D010455:Peptides / Q000032:analysis / Q000276:immunology; D021382:Protein Sorting Signals; D020080:Tandem Repeat Sequences
D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018396:Mucin-1; D010455:Peptides; D021382:Protein Sorting Signals