IDENTIFICATION OF AN HLA-A11-RESTRICTED EPITOPE FROM THE TANDEM REPEAT DOMAIN OF THE EPITHELIAL TUMOR-ANTIGEN MUCIN

Epithelial cell mucin encoded by the MUC-1 gene is overexpressed and a berrantly glycosylated on pancreatic, breast, and ovarian cancers as w ell as on multiple myelomas. It is recognized by patients' Ab and by T cells derived from tumor-draining lymph nodes. The T cell recognition is not MHC restricted and is specific for an epitope previously local ized to the immunodominant tandem repeat region of the native mucin mo lecule. In search of possible MHC-restricted epitopes in the same immu nodominant region, we synthesized a panel of overlapping, nine-amino a cid long peptides spanning the MUC-1 tandem repeat and first examined their binding to specific human MHC class I molecules using two indepe ndent flow cytometry-based assay systems. This approach identified one peptide, p9-17 (STAPPAHGV), that bound to HLA-A1, -A2.1, -A3, and -A1 1. Measurements of the affinity of binding to each of these alleles, u sing a quantitative molecular binding assay, indicated that only the r elative binding affinity to HLA-A11 was close to immunogenic values. W e tested the immunogenicity of p9-17 in vitro. We detected a secondary T cell response specific for p9-17 in lymph nodes from an HLA-A11 bre ast cancer patient. Moreover, CTL specific for p9-17 peptide could be generated from PBL in several healthy HLA-A11 donors by primary in vit ro stimulation.