title: Mapping and binding analysis of peptides derived from the tumor-associated antigen survivin for eight HLA alleles.
abstract: There is considerable interest in developing immunotherapeutic approaches to elicit tumor-specific CTL responses in cancer patients. Epitope-based approaches aim to deliver the antigenic peptides or epitopes recognized by CTLs rather than the intact tumor antigen. Many tumor-associated proteins are nonmutated self proteins for which the dominant peptide epitopes are usually poorly immunogenic. The subdominant epitopes, however, can elicit robust T cell responses if optimized for their ability to bind to class I MHC molecules. Only the epitopes for a few tumor antigens expressed in human cancers have been defined to this level, mainly for technical reasons. The means to rapidly screen and characterize the binding of epitopes derived from complex tumor-associated antigens is an important enabling technology. Here, we have used the high-throughput technology iTopia to identify those peptides derived from the tumor-associated antigen survivin that bind 8 class I alleles. A library of overlapping nonamers spanning the length of the survivin protein was initially screened for peptides capable of binding each allele. Nineteen HLA-A*0201, zero HLA-A*0101, seven HLA-A*0301, twelve HLA-A*1101, twenty-four HLA-A*2402, six HLA-B*0702, six HLA-B*0801, and eight HLA-B*1501 binding peptides were identified based on an arbitrary cutoff. Peptides capable of binding a given allele were further characterized by their affinity for MHC class I molecules and by the rate of dissociation of the complex. This information should help guide functional studies and future epitope-based immunotherapies.
authors.affiliation: Department of Immunotherapeutics, Purdue Pharma, Cranbury, NJ, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Bachinsky
authors.forename: Darlene E
authors.initials: DE
authors.lastname: Guillen
authors.forename: Sima R
authors.initials: SR
authors.lastname: Patel
authors.forename: Judith
authors.initials: J
authors.lastname: Singleton
authors.forename: Chaoyuan
authors.initials: C
authors.lastname: Chen
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Soltis
authors.forename: Lynda G
authors.initials: LG
authors.lastname: Tussey
mesh_terms: D000483:Alleles; D000951:Antigens, Neoplasm; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D010449:Peptide Mapping; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D006680:HLA Antigens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D000077022:Survivin