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.
Article|
January 01 1994
Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas.
F V Cromme,
F V Cromme
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
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J Airey,
J Airey
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
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M T Heemels,
M T Heemels
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
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H L Ploegh,
H L Ploegh
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
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P J Keating,
P J Keating
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
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P L Stern,
P L Stern
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
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C J Meijer,
C J Meijer
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
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J M Walboomers
J M Walboomers
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
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F V Cromme
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
J Airey
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
M T Heemels
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
H L Ploegh
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
P J Keating
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
P L Stern
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
C J Meijer
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
J M Walboomers
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Online Issn: 1540-9538
Print Issn: 0022-1007
J Exp Med (1994) 179 (1): 335–340.
Citation
F V Cromme, J Airey, M T Heemels, H L Ploegh, P J Keating, P L Stern, C J Meijer, J M Walboomers; Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas.. J Exp Med 1 January 1994; 179 (1): 335–340. doi: https://doi.org/10.1084/jem.179.1.335
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