Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas.
dc.contributor.author | Cromme, F V | |
dc.contributor.author | Airey, J | |
dc.contributor.author | Heemels, M T | |
dc.contributor.author | Ploegh, H L | |
dc.contributor.author | Keating, P J | |
dc.contributor.author | Stern, Peter L | |
dc.contributor.author | Meijer, C J | |
dc.contributor.author | Walboomers, J M | |
dc.date.accessioned | 2010-04-09T10:51:17Z | |
dc.date.available | 2010-04-09T10:51:17Z | |
dc.date.issued | 1994-01-01 | |
dc.identifier.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. | en |
dc.identifier.issn | 0022-1007 | |
dc.identifier.pmid | 8270878 | |
dc.identifier.uri | http://hdl.handle.net/10541/96118 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.subject | Uterine Cervical Cancer | en |
dc.subject.mesh | ATP-Binding Cassette Transporters | |
dc.subject.mesh | Antibody Specificity | |
dc.subject.mesh | Biological Transport | |
dc.subject.mesh | Carrier Proteins | |
dc.subject.mesh | Female | |
dc.subject.mesh | HLA Antigens | |
dc.subject.mesh | Histocompatibility Antigens Class I | |
dc.subject.mesh | Histocompatibility Antigens Class II | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Immune Sera | |
dc.subject.mesh | Uterine Cervical Neoplasms | |
dc.title | Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. | en |
dc.type | Article | en |
dc.contributor.department | Department of Pathology, Free University Hospital, Amsterdam, The Netherlands. | en |
dc.identifier.journal | The Journal of Experimental Medicine | en |
html.description.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. |