| An antigen was identified from a mouse mammary tumor. Previously other mammary tumor antigens were reported to be recognized by CTL but it has been difficult to identify the peptides triggering their response. This is the first report of the MHC Class I natural tumor peptide antigen identified directly from the mouse mammary tumor. The peptides isolated from MHC Class I receptor of normal mammary gland were compared to the peptides from this tumor. These comparisons indicated several peptides, specific to the tumor (1008, 1084, 1119, 1185, 1241, 1262 m/z) and a few specific for the normal mammary gland (1163, 1235.3, 1220). The second dimension RP-HPLC separated the most abundant tumor specific (1186 m/z) and normal-specific (1235.3 m/z) peptides. The dominant immuno-recognized tumor peptide antigen was completely sequenced after RP-HPLC purification by combination of enzymatic digestion and mass spectrometry MALDI. This peptide sequence ECARHFRQH is most homologous to the oncogene proteins Wnt-1 or Wnt-2, which are host regulatory proteins commonly reported to be synthesized under control of the MMTV virus. This was the most abundant peptide of the tumor peptides and was recognized by CTL derived from mice bearing breast tumor. This suggests that antigenic CTL responses are indeed directed at a dominant tumor peptide antigen presented in the context of MHC I on the cell surface of the tumor cells. This peptide-induced lysis by CTL of tumor-bearing animals suggests that it may be promising for use in peptide-based anti breast tumor vaccines. Since it originated from the conserved region of the most commonly reported protein in mouse and many human breast tumors, it is tempting to speculate that this common antigen might be used for breast cancer vaccination across species. This work confirms that indeed the altered cellular protein expressed in abundance is also presented in large number in the form of the peptide in the MHC Class I complexes to CTL. |
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