Secondary anchor substitutions in an HLA-A*0201-restricted T-cell epitope derived from Her-2/neu

Mol Immunol. 2007 Jan;44(4):322-31. doi: 10.1016/j.molimm.2006.02.027. Epub 2006 Apr 4.


We investigated analogues of GP2 (IISAVVGIL), an HLA-A*0201-restricted T-cell epitope derived from residues 654-662 in the tumor-associated antigen (TAA) Her-2/neu. One limiting factor of GP2 is its poor affinity for HLA-A*0201. Conformational analysis revealed the P5-P7 region in GP2 appears to be linked to the stability of P9 side chain interaction with the MHC molecule. To identify variants of GP2 with enhanced presentation to HLA-A*0201, we tested V6S, V6T, V6Q, G7P, G7F, T6F7, and Q6F7 for their capacity to stabilize cell surface HLA-A*0201 molecules. Of the mono-substituted variants, V6Q and G7F exhibited superior stabilization as compared to GP2. Molecular dynamics simulations suggest the improved binding can be attributed to concerted motions in the central and C-terminal regions of the peptide. These data support the notion that amino acids in HLA-A*0201 epitopes may be inter-dependent. Priming HLA-A*0201 transgenic mice with G7F-loaded syngeneic dendritic cells stimulated mouse T cells to produce a higher level of INFgamma than mice immunized with GP2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte / chemistry*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / metabolism
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / genetics
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Molecular
  • Molecular Conformation
  • Protein Binding
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / genetics
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology


  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • Histocompatibility Antigens Class I
  • Receptor, ErbB-2