Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas.

2.50
Hdl Handle:
http://hdl.handle.net/10541/96118
Title:
Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas.
Authors:
Cromme, F V; Airey, J; Heemels, M T; Ploegh, H L; Keating, P J; Stern, Peter L; Meijer, C J; Walboomers, J M
Abstract:
Malignant tumor cells can escape CD8+ cytotoxic T cell killing by downregulating class I major histocompatibility complex (MHC) expression. Stable class I MHC surface expression requires loading of the heavy chain/light chain dimer with antigenic peptide, which is delivered to class I MHC molecules in the endoplasmic reticulum by the presumed peptide transporter, encoded by the transporter associated with antigen presentation (TAP) 1 and 2 genes. We have investigated whether loss of class I MHC expression frequently observed in different cancers could result from interference with TAP function. A polyclonal antiserum, raised against a bacterial glutathione S-transferase/human TAP-1 fusion protein, was used for the immunohistochemical analysis of TAP-1 expression in 76 cervical carcinomas. Results showed loss of TAP-1 expression in neoplastic cells in 37 out of 76 carcinomas. Immunohistochemical double staining procedures in combination with HLA-specific antibodies revealed congruent loss at the single cell level of TAP-1 and HLA-A/B expression in 28 out of 37 carcinomas. The remaining samples expressed HLA(-A) in the absence of TAP-1 (n = 6) or showed loss of HLA(-A/B) while TAP-1 was expressed (n = 3). These data strongly indicate that inhibition of peptide transport by downregulation of TAP-1 is a potential strategy of malignant cells to evade immune surveillance.
Affiliation:
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Citation:
Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. 1994, 179 (1):335-40 J. Exp. Med.
Journal:
The Journal of Experimental Medicine
Issue Date:
1-Jan-1994
URI:
http://hdl.handle.net/10541/96118
PubMed ID:
8270878
Type:
Article
Language:
en
ISSN:
0022-1007
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorCromme, F Ven
dc.contributor.authorAirey, Jen
dc.contributor.authorHeemels, M Ten
dc.contributor.authorPloegh, H Len
dc.contributor.authorKeating, P Jen
dc.contributor.authorStern, Peter Len
dc.contributor.authorMeijer, C Jen
dc.contributor.authorWalboomers, J Men
dc.date.accessioned2010-04-09T10:51:17Z-
dc.date.available2010-04-09T10:51:17Z-
dc.date.issued1994-01-01-
dc.identifier.citationLoss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. 1994, 179 (1):335-40 J. Exp. Med.en
dc.identifier.issn0022-1007-
dc.identifier.pmid8270878-
dc.identifier.urihttp://hdl.handle.net/10541/96118-
dc.description.abstractMalignant tumor cells can escape CD8+ cytotoxic T cell killing by downregulating class I major histocompatibility complex (MHC) expression. Stable class I MHC surface expression requires loading of the heavy chain/light chain dimer with antigenic peptide, which is delivered to class I MHC molecules in the endoplasmic reticulum by the presumed peptide transporter, encoded by the transporter associated with antigen presentation (TAP) 1 and 2 genes. We have investigated whether loss of class I MHC expression frequently observed in different cancers could result from interference with TAP function. A polyclonal antiserum, raised against a bacterial glutathione S-transferase/human TAP-1 fusion protein, was used for the immunohistochemical analysis of TAP-1 expression in 76 cervical carcinomas. Results showed loss of TAP-1 expression in neoplastic cells in 37 out of 76 carcinomas. Immunohistochemical double staining procedures in combination with HLA-specific antibodies revealed congruent loss at the single cell level of TAP-1 and HLA-A/B expression in 28 out of 37 carcinomas. The remaining samples expressed HLA(-A) in the absence of TAP-1 (n = 6) or showed loss of HLA(-A/B) while TAP-1 was expressed (n = 3). These data strongly indicate that inhibition of peptide transport by downregulation of TAP-1 is a potential strategy of malignant cells to evade immune surveillance.en
dc.language.isoenen
dc.subjectUterine Cervical Canceren
dc.subject.meshATP-Binding Cassette Transporters-
dc.subject.meshAntibody Specificity-
dc.subject.meshBiological Transport-
dc.subject.meshCarrier Proteins-
dc.subject.meshFemale-
dc.subject.meshHLA Antigens-
dc.subject.meshHistocompatibility Antigens Class I-
dc.subject.meshHistocompatibility Antigens Class II-
dc.subject.meshHumans-
dc.subject.meshImmune Sera-
dc.subject.meshUterine Cervical Neoplasms-
dc.titleLoss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, Free University Hospital, Amsterdam, The Netherlands.en
dc.identifier.journalThe Journal of Experimental Medicineen

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