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Priming of immune responses against transporter associated with antigen processing (TAP)‐deficient tumours: tumour direct priming
Author(s) -
Li XiaoLin,
Zhang Dongqing,
Knight David,
Odaka Yoshinobu,
Glass Jonathan,
Mathis J. Michael,
Zhang QianJin
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03127.x
Subject(s) - priming (agriculture) , transporter associated with antigen processing , biology , major histocompatibility complex , immune system , immunology , antigen , mhc class i , immunity , t cell , cancer research , botany , germination
Summary 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.