Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas.
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.
Cromme
F V
FV
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Airey
J
J
Heemels
M T
MT
Ploegh
H L
HL
Keating
P J
PJ
Stern
P L
PL
Meijer
C J
CJ
Walboomers
J M
JM
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000918:Antibody Specificity; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera; D002583:Uterine Cervical Neoplasms / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007106:Immune Sera; C073119:TAP1 protein, human