SEQUENCE MOTIFS OF HUMAN HER-2 PROTOONCOGENE IMPORTANT FOR PEPTIDE BINDING TO HLA-A2

FISK, B; CHESAK, B; IOANNIDES, MG; WHARTON, JT; IOANNIDES, CG

dc.contributor.author	FISK, B	en
dc.contributor.author	CHESAK, B	en
dc.contributor.author	IOANNIDES, MG	en
dc.contributor.author	WHARTON, JT	en
dc.contributor.author	IOANNIDES, CG	en
dc.date.accessioned	2014-03-01T01:42:56Z
dc.date.available	2014-03-01T01:42:56Z
dc.date.issued	1994	en
dc.identifier.issn	1019-6439	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/23989
dc.subject	HER-2	en
dc.subject	HLA-A2	en
dc.subject	T-CELL EPITOPES	en
dc.subject.classification	Oncology	en
dc.subject.other	CYTOTOXIC LYMPHOCYTES-T	en
dc.subject.other	TUMOR-INFILTRATING LYMPHOCYTES	en
dc.subject.other	VIRUS MATRIX PROTEIN	en
dc.subject.other	CLASS-I	en
dc.subject.other	CELL EPITOPES	en
dc.subject.other	MHC MOLECULES	en
dc.subject.other	INVITRO	en
dc.subject.other	INDUCTION	en
dc.subject.other	MUTANT	en
dc.subject.other	TRANSPORT	en
dc.title	SEQUENCE MOTIFS OF HUMAN HER-2 PROTOONCOGENE IMPORTANT FOR PEPTIDE BINDING TO HLA-A2	en
heal.type	journalArticle	en
heal.language	English	en
heal.publicationDate	1994	en
heal.abstract	Tumor progression and metastasis are often associated with overexpression of specific cellular proteins. In 1991, we introduced a hypothesis that epitopes of nonmutated overexpressed proteins can be targets of a specific cellular immune response against tumor mediated by T cells (Mol Carcinogen 6: 77-81, 1992) and that, when T cell epitopes are present, distinction between tumor immunity/autoimmunity and unresponsiveness can be predicated on the protein concentration as a limiting factor of epitope supply. In support of this hypothesis, we demonstrated that CTL from patients with ovarian tumors which overexpress HER-2 proto-oncogene can recognize both autologous tumor and synthetic analogs of a specific epitope from HER-2, which was identified based on the convergence of all criteria for selection of HLA-A2 associated epitopes recognized by T cells. In this study, we identified all epitopes in HER-2 containing nonapeptides with HLA-A2 anchors. Of these, analysis of potential amphiphilic sites identified both sequences and specific mutations that positively affected the reactivity of conformationally dependent HLA-A2 specific mAb which served as an indication of HER-2 peptide binding. We also report the in vitro induction of cellular responses to these peptides by PBMC from healthy HLA-A2+ volunteers as an indication of their ability to stimulate/ restimulate pre-existing T cell responses to HER-2. The peptides induced proliferative responses in one of four donors tested and CTL responses (one of three peptides tested in two of three donors). This strategy may allow selection of immunogenic HER-2 peptides and elucidation of mechanisms operating in induction of tolerance to defined epitopes on self-proteins.	en
heal.publisher	INT JOURNAL ONCOLOGY	en
heal.journalName	INTERNATIONAL JOURNAL OF ONCOLOGY	en
dc.identifier.isi	ISI:A1994NR64300007	en
dc.identifier.volume	5	en
dc.identifier.issue	1	en
dc.identifier.spage	51	en
dc.identifier.epage	63	en