Ljunggren H G, Van Kaer L, Ploegh H L, Tonegawa S
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6520-4. doi: 10.1073/pnas.91.14.6520.
We have analyzed the specificity and function of natural killer (NK) cells in mice with a homozygous deletion of the major histocompatibility complex (MHC)-encoded transporter gene associated with MHC class I-restricted antigen presentation (Tap-1). These mice express very low levels of class I molecules at the cell surface, and these molecules are either devoid of peptide or occupied only by TAP-independent peptides. NK cells in Tap-1 -/- mice, through normal in number, appeared tolerant toward autologous Tap-1 -/- Con A-activated blasts, Tap-1 -/- as well as allogeneic BALB/c bone marrow cells, and RMA-S tumor cell grafts. In contrast, they killed YAC-1 cells as efficiently as did NK cells from wild-type mice. Defective Tap-1 expression was sufficient to render nontransformed target cells sensitive to NK cell-mediated lysis. It is concluded that proper expression of TAP molecules is necessary for normal development of NK cells, as well as for rendering target cells resistant to NK cell-mediated lysis. These results support the hypothesis that class I molecules of the MHC influence the sensitivity of target cells to lysis by NK cells, as well as the development of the NK cell repertoire.
我们分析了主要组织相容性复合体（MHC）编码的与MHC I类限制性抗原呈递相关的转运体基因（Tap-1）纯合缺失小鼠中自然杀伤（NK）细胞的特异性和功能。这些小鼠在细胞表面表达极低水平的I类分子，且这些分子要么不含肽段，要么仅被不依赖TAP的肽段占据。Tap-1 -/-小鼠中的NK细胞数量正常，对自体Tap-1 -/-伴刀豆球蛋白A激活的母细胞、Tap-1 -/-以及同种异体BALB/c骨髓细胞和RMA-S肿瘤细胞移植表现出耐受。相反，它们杀伤YAC-1细胞的效率与野生型小鼠的NK细胞相同。Tap-1表达缺陷足以使未转化的靶细胞对NK细胞介导的裂解敏感。结论是，TAP分子的正常表达对于NK细胞的正常发育以及使靶细胞抵抗NK细胞介导的裂解是必要的。这些结果支持了这样的假说，即MHC的I类分子影响靶细胞对NK细胞裂解的敏感性以及NK细胞库的发育。
