Kung S K, Su R C, Graham J J, Chamberlain J W, Miller R G
Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Canada.
J Immunol. 1998 Jan 15;160(2):674-80.
We have investigated the capacity of human MHC class I HLA-B gene products, HLA-B27, -B7 (fully human), and -B7kb (human-mouse hybrid consisting of the alpha1 and alpha2 domains of HLA-B7, and the alpha3 and cytoplasmic domains of mouse H-2Kb), expressed on mouse NK cells during ontogeny to influence NK recognition of otherwise syngeneic mouse target cells. Despite a high level of surface expression of the transgene (comparable to that of endogeneous H-2DbKb molecules), the direct killing of YAC-1 targets, and the killing of P815 targets in a redirected lysis assay, the NK effectors of these transgenic mice could not mediate hybrid resistance-like killing of nontransgenic C57BL/6 target cells either in vitro or in vivo. Splenocytes from B6-B27 mice could be used to generate CTL lines against a B27-binding peptide, implying that T cells restricted by HLA-B27 developed during ontogeny. NK cells from B6-B27 could lyse B6-B27 Con A lymphoblasts pulsed with Db-binding peptide but not B27-binding peptides. Taken together, our results show that these human HLA-B transgene products cannot function as class I MHC "self" elements for mouse NK cells, even when present throughout ontogeny.
我们研究了在个体发育过程中表达于小鼠自然杀伤（NK）细胞上的人类主要组织相容性复合体（MHC）I类HLA - B基因产物HLA - B27、- B7（完全人源）和 - B7kb（由HLA - B7的α1和α2结构域以及小鼠H - 2Kb的α3和胞质结构域组成的人 - 鼠杂交体）影响NK细胞对原本同基因小鼠靶细胞识别的能力。尽管转基因在表面有高水平表达（与内源性H - 2DbKb分子相当），在YAC - 1靶细胞的直接杀伤以及重定向裂解试验中对P815靶细胞的杀伤方面表现良好，但这些转基因小鼠的NK效应细胞在体外或体内均不能介导对非转基因C57BL/6靶细胞的类似杂种抗性的杀伤。来自B6 - B27小鼠的脾细胞可用于产生针对与B27结合肽的细胞毒性T淋巴细胞（CTL）系，这意味着受HLA - B27限制的T细胞在个体发育过程中得以发育。来自B6 - B27的NK细胞可裂解用Db结合肽脉冲处理的B6 - B27伴刀豆球蛋白A（Con A）淋巴母细胞，但不能裂解用B27结合肽处理的细胞。综上所述，我们的结果表明，即使这些人类HLA - B转基因产物在整个个体发育过程中都存在，它们也不能作为小鼠NK细胞的I类MHC“自身”元件发挥作用。
