Priming of immune responses against transporter associated with antigen processing (TAP)-deficient tumours: tumour direct priming.
We previously showed that introduction of transporter associated with antigen processing (TAP) 1 into TAP-negative CMT.64, a major histocompatibility complex class I (MHC-I) down-regulated mouse lung carcinoma cell line, enhanced T-cell immunity against TAP-deficient tumour cells. Here, we have addressed two questions: (1) whether such immunity can be further augmented by co-expression of TAP1 with B7.1 or H-2K(b) genes, and (2) which T-cell priming mechanism (tumour direct priming or dendritic cell cross-priming) plays the major role in inducing an immune response against TAP-deficient tumours. We introduced the B7.1 or H-2K(b) gene into TAP1-expressing CMT.64 cells and determined which gene co-expressed with TAP1 was able to provide greater protective immunity against TAP-deficient tumour cells. Our results show that immunization of mice with B7.1 and TAP1 co-expressing but not H-2K(b) and TAP1 co-expressing CMT.64 cells dramatically augments T-cell-mediated immunity, as shown by an increase in survival of mice inoculated with live CMT.64 cells. In addition, our results suggest that induction of T-cell-mediated immunity against TAP-deficient tumour cells could be mainly through tumour direct priming rather than dendritic cell cross-priming as they show that T cells generated by tumour cell-lysate-loaded dendritic cells recognized TAP-deficient tumour cells much less than TAP-proficient tumour cells. These data suggest that direct priming by TAP1 and B7.1 co-expressing tumour cells is potentially a major mechanism to facilitate immune responses against TAP-deficient tumour cells.
Li
Xiao-Lin
XL
Department of Cellular Biology and Anatomy, Gene Therapy Program, Louisiana State University Health Sciences Center, Kings Hwy, Shreveport, LA 71130, USA.
Zhang
Dongqing
D
Knight
David
D
Odaka
Yoshinobu
Y
Glass
Jonathan
J
Mathis
J Michael
JM
Zhang
Qian-Jin
QJ
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D045142:Cross-Priming; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014162:Transfection; D019076:Transgenes / Q000235:genetics*
D018528:ATP-Binding Cassette Transporters; D018122:B7-1 Antigen; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C477327:transporter associated with antigen processing (TAP)