Generation of CD8(+) T cells specific for transporter associated with antigen processing deficient cells

被引:39
|
作者
Wolpert, EZ [1 ]
Petersson, M [1 ]
Chambers, BJ [1 ]
Sandberg, JK [1 ]
Kiessling, R [1 ]
Ljunggren, HG [1 ]
Karre, K [1 ]
机构
[1] KAROLINSKA HOSP,RADIUMHEMMET,DEPT EXPT ONCOL,S-17176 STOCKHOLM,SWEDEN
关键词
D O I
10.1073/pnas.94.21.11496
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cells with impaired transporter associated with antigen processing (TAP) function express low levels of cell surface major histocompatibility complex (MHC) class I molecules, and are generally resistant to lysis by MHC class I restricted cytotoxic T lymphocytes (CTLs). Here we report the generation of MHC class I restricted CD8(+) CTLs that surprisingly require target cell TAP deficiency for efficient recognition. C57BL/6 (B6) mice immunized with syngenic B7-1 (CD80) expressing TAP-deficient cells generated a potent CTL response against both TAP-deficient RMA-S tumor cells and TAP-deficient Con A blasts, whereas the corresponding TAP-expressing target cells were considerably less susceptible or resistant to lysis. The CTL epitopes recognized were expressed also by the human TAP-deficient cell line T2, transfected with appropriate MHC class I molecules. B6 mice immunized with B7-1-transfected TAP-deficient RMA-S cells were protected from outgrowth of a subsequent RMA-S tumor challenge. These findings are discussed in relation to the biochemical nature of MHC class I dependent CTL epitopes associated with impaired TAP function, as well as implications for immunotherapy and autoimmunity.
引用
收藏
页码:11496 / 11501
页数:6
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