title: Altered decamer and nonamer from an HLA-A0201-restricted epitope of Survivin differentially stimulate T-cell responses in different individuals.
abstract: Survivin is a universal tumor antigen that is being currently targeted in vaccine approaches against cancer. Our study here examined the immunogenicity of a novel variant of an HLA-A0201-binding decamer peptide from region 95 to 104 of Survivin (ELMLGEFLKL) with a T→M modification at position 3 in the peptide. We found that this new modified 10-mer peptide had enhanced HLA-A0201 binding and induced a stronger T-cell response over its wild type counterpart peptide (ELTLGEFLKL) in select HLA-A0201(+) normal donors. In addition, when compared to the previously characterized altered 96-104 peptide (LMLGEFLKL) from the same region of Survivin currently used in vaccine trials, we found that both peptides had similar immunogenicity, but donor T cells preferentially reacted strongly to either one or the other, but not strongly to both. These results suggest that these two closely related Survivin peptides yield distinct T-cell responses and that most individuals dominantly respond to one or the other altered peptide. We also found a novel association between positive reactivity to the new altered decamer Survivin peptide in some individuals and their expression of the HLA-C0701 allele along with HLA-A0201. Thus, vaccinating with both the 10-mer and 9-mer peptides would be required to immunize a maximum number of individuals in the HLA-A0201(+) population and could lead to more consistent T-cell responses against this region of Survivin.
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: Chantale
authors.initials: C
authors.lastname: Bernatchez
authors.forename: Kuichin
authors.initials: K
authors.lastname: Zhu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.forename: Helen
authors.initials: H
authors.lastname: Andersson
authors.forename: Constantin
authors.initials: C
authors.lastname: Ionnides
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez-Vina
authors.forename: Pedro
authors.initials: P
authors.lastname: Cano
authors.forename: Laurence
authors.initials: L
authors.lastname: Cooper
authors.forename: James
authors.initials: J
authors.lastname: Abbruzzese
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: David Z
authors.initials: DZ
authors.lastname: Chang
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Radvanyi
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology*; D008958:Models, Molecular; D010455:Peptides / Q000276:immunology; D011485:Protein Binding; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D051034:Inhibitor of Apoptosis Proteins; D010455:Peptides; D000077022:Survivin