Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus
Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus
复制标题
能够阻断细胞毒性 T 细胞功能的小鼠同种抗体。
DOI：
--
复制
发表时间：
1979
影响因子：
15.3
通讯作者：
D. Sachs
中科院分区：
文献类型：
--
作者：
N. Shinohara;D. Sachs
为了生产细胞毒性 T 细胞受体的同种抗体，在不同品系组合的小鼠中制备了超免疫抗淋巴细胞抗血清，并测试了它们在 T 杀伤细胞水平上缺乏补体的情况下阻断同种异体细胞介导的淋巴细胞毒性 (CML) 的能力。大多数血清未能表现出任何显着且可重复的抑制作用。然而，在C3H抗B10.BR抗血清中，发现一些血清能够显着抑制CML。这种效应归因于抗体与杀伤细胞群而不是靶细胞反应，因为血清抑制 B10 抗 C3H CML，但不抑制 C3H 抗 b10 CML。在测试的小鼠品系中，A/J、BALB/c、B10和B6品系对血清的抑制作用敏感，而AKR、CBA、C3H和DBA/2品系不敏感。杀伤细胞对抑制作用的敏感性与Lyt-2.2抗原的菌株分布密切相关。在补体存在下，这些相同的血清对 AKR、BALB/c、B10 和 DBA/2 菌株的 100% 脾细胞具有毒性，且细胞毒性滴度相当。因此，血清的抑制活性不能用高滴度抗体的非特异性作用来解释。为了研究负责阻断作用的抗原与Lyt-2连锁基因之间的关系，测试了来自Lyt-2同源菌株的杀伤细胞，并在适当的同源菌株组合中产生了常规抗Lyt-2.2抗血清。来自 B6 而非 B6.Ly2.1 动物的杀伤细胞对抑制性 C3H 抗 B10.BR 血清的阻断作用显着敏感。常规抗Lyt.2.2血清确实产生CML阻断，尽管这种阻断与抗Lyt-2.2细胞毒性滴度之间没有明显相关性。因此，这些结果表明负责阻断杀伤细胞的靶分子是由与Lyt-2密切相关或相同的基因编码或调节的。
In an attempt to produce allonatibodies to cytotoxic T-cell receptors, hyperimmune anti-lymphocyte antisera have been raised in mice of various strain combinations, and have been tested for their ability to block allogeneic cell-mediated lymphocytotoxicity (CML) in the absence of complement at the T killer cell level. Most of the sera failed to show any significant and reproducible inhibitory effects. However, among C3H anti-B10.BR antisera, some sera were found to be capable of significantly inhibiting CML. This effect was attributable to antibodies reacting with the killer population rather than the target cells, because the sera inhibited B10 anti-C3H CML but not C3H anti-b10 CML. Among mouse strains tested, A/J, BALB/c, B10, and B6 strains were sensitive to the inhibitory effect of the sera whereas AKR, CBA, C3H, and DBA/2 strains were insensitive. The sensitivity of killer cells to the inhibitory effect correlated well with the strain distribution of the Lyt-2.2 antigen. In the presence of complement, these same sera were toxic to 100% of spleen cells of AKR, BALB/c, B10, and DBA/2 strains, with comparable cytotoxic titers. Thus, the inhibitory activity of the sera could not be explained by nonspecific effects of high-titered antibodies. To study the relationship between the antigen(s) responsible for the blocking effect and Lyt-2-linked genes, killer cells from Lyt-2 congenic strains were tested and conventional anti-Lyt-2.2 antisera were raised in an appropriate congenic strain combination. Killer cells from B6, but not from B6.Ly2.1 animals, were significantly sensitive to the blocking effects of the inhibitory C3H anti-B10.BR sera. The conventional anti-Lyt.2.2 sera did produce CML blocking, although there was no apparent correlation between such blocking and the anti-Lyt-2.2 cytotoxic titer. These results thus indicate that the target molecules responsible for blocking of killer cells are encoded or regulated by genes that are closely linked to or identical with Lyt-2.