STRUCTURE OF A TUMOR-ASSOCIATED ANTIGEN CONTAINING A TANDEMLY REPEATED IMMUNODOMINANT EPITOPE

Human mucins are T or S glycosylated tandem repeat proteins. In breast cancer, mucins become under or unglycosylated Two-dimensional nuclear magnetic resonance experiments are performed on chemically synthesize d mucin tandem repeat polypeptides, (PDTRPAPGSTAPPAHGVTSA)n in the ung lycosylated form for n = 1,3 where (APDTR) constitutes the antigenic s ites for the antibodies isolated from the tumors in the breast cancer patients. These studies demonstrate how the tandem repeats assemble in space giving rise to the overall tertiary structure, and the local st ructure and presentation of the antigenic site (APDTR) at the junction of two neighboring repeats. The NMR data reveal repeating knob-like s tructures connected by extended spacers. The knobs protrude away from the long-axis of Muc-1 and the predominant antigenic site (APDTR) form s the accessible tip of the knob. Multiple tandem repeats enhance the rigidity and presentation of the knob-like structures.