The biologic significance of alloreactivity. The ontogeny of T-cell sets specific for alloantigens or modified self antigens.
The biologic significance of alloreactivity. The ontogeny of T-cell sets specific for alloantigens or modified self antigens.
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同种异体反应性的生物学意义。 T细胞的个体发育集对同种抗原或改良的自抗原。
DOI：
10.1084/jem.148.5.1414
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发表时间：
1978-11-01
影响因子：
15.3
通讯作者：
Cantor, H
中科院分区：
文献类型：
--
作者：
Burakoff, S J;Finberg, R;Glimcher, L;Lemonnier, F;Benacerraf, B;Cantor, H
我们已经分析了T细胞对淋巴细胞的反应性的细胞基础，表达主要组织相容性复合体（MHC）的产品是凭借多态性（同种异体抗原）或由于化学品或病毒的修饰外来。我们发现，在个体发育早期，针对三硝基苯基（TNP）偶联的自体MHC产物和同种异体MHC产物的前杀伤活性存在于相同的（Ly 123（+））T细胞库中;后来在个体发育中，同种异体反应性被投资于Ly 23细胞，当被激活时，溶解TNP偶联的自体细胞以及适当的同种异体靶细胞。我们证明，Ly 123（+）T细胞在体外的刺激与化学灭活仙台病毒包被的自体细胞的结果形成Ly 23（+）细胞溶解性T淋巴细胞（CTL），特异性裂解病毒修饰的自体靶细胞和未修饰的同种异体靶细胞。这些结果表明以下模型来解释成年动物中大量同种异体反应性T细胞克隆的存在：与外源物质（如病毒）相关的自体MHC抗原对Ly 123细胞的持续刺激导致Ly 23记忆后代的形成，该后代携带识别由于遗传多态性而为外源的MHC产物（同种异体抗原）的受体。一般而言，这些研究表明同种异体攻击（如CTL应答中Ly 23细胞所表现的）反映了生理学相关抗原之间的高度交叉刺激，例如，与自身MHC产物相关的病毒决定簇，以及MHC的生物学上不相关的等位基因变体。
We have analyzed the cellular basis of T-cell reactivity against lymphocytes expressing major histocompatibility complex (MHC) products that are foreign by virtue of polymorphism (alloantigens) or because of modification by chemicals or viruses. We find that early in ontogeny, prekiller activity against both trinitrophenyl (TNP)-coupled autologous MHC products and allogeneic MHC products resides in the same (Ly123(+)) T-cell pool; later in ontogeny alloreactivity is invested in Ly23 cells which, when activated, lyse TNP-coupled autologous cells as well as appropriate allogeneic target cells. We demonstrate that stimulation of Ly123(+) T cells in vitro by autologous cells coated with chemically-inactivated Sendai virus results in the formation of Ly23(+) cytolytic T lymphocytes (CTL) that specifically lyse both virus modified autologous target cells and unmodified allogeneic target cells. These results suggest the following model to account for the presence of large numbers of alloreactive T-cell clones in adult animals: continuous stimulation of Ly123 cells by autologous MHC antigens associated with foreign materials such as a virus results in the formation of Ly23 memory progeny carrying receptors that recognize MHC products that are foreign due to genetic polymorphism (alloantigens). In general, these studies indicate that alloaggression (as manifest by Ly23 cells in the CTL response) reflects a high degree of cross stimulation between physiologically relevant antigens, e.g., viral determinants associated with self MHC products, and biologically irrelevant allelic variants of the MHC.