Changes in an HER-2 peptide upregulating HLA-A2 expression affect both conformational epitopes and CTL recognition: implications for optimization of antigen presentation and tumor-specific CTL induction.

摘要: The HER-2/neu protooncogene (HER-2) is overexpressed in a significant number of breast and ovarian tumors. Peptides HER-2 sequence were recently found to reconstitute recognition cytotoxic T lymphocytes (CTLs) from tumor-associated (TALs) tumor-infiltrating (TILs) lymphocytes, indicating that they natural epitopes recognized by CTLs on HLA-A2+ Because an important antigen (Ag) for tumor-specific CTL induction the immunogenicity peptides dependent their presentation as stable complexes with HLA-A2, we identified high low stabilizing activity folate-binding protein (FBP). Distinct patterns region positions (P)3-P5 P1 (HSA) (LSA) ability. A low-HLA-A2-affinity peptide, epitope, was be permissive substitutions enhanced HLA-A2-stabilizing ability conserved recognition. In contrast, P3-P5 not changes. We conclude selective permissivity P9 tumor epitope may have implications optimization Ag presentation, "neoantigenicity" self-antigens, aiming toward tumor-reactive defined affinity specificity target Ags.