HISTOCOMPATIBILITY-LINKED IMMUNE-RESPONSE GENES

HISTOCOMPATIBILITY-LINKED IMMUNE-RESPONSE GENES
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DOI:
10.1126/science.175.4019.273
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发表时间:
1972-01-01
期刊:
影响因子:
56.9
通讯作者:
MCDEVITT, HO
MCDEVITT, HO
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BENACERR.B;MCDEVITT, HO

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图1。H-2基因座的组织示意图,箭头表示杂交导致重组H-2等位基因的近端位置。顶部的箭头表示H-2‘和H-2b之间的一组5个反向交叉产生H-2和H-2’重组等位基因。这五个重组等位基因都将ir - 1定位在交叉事件的右侧。底部的三个箭头表示H-2d和H-2k之间的一组三个互反交叉,产生H-2a-Ssl, H-20-Ss'和H-2-Ssh。同样,ir - 1位于这些交叉点的右侧。H-2t-Ss‘是由H-2^-Ss’和H-2'的交叉得到的,Ir-i位于该交叉的左边。h -2‘来源于h -2’和H-2q的交叉,在这个交叉事件中有一个外部标记(brachyury, T),它确定了交叉是一个单一的交叉事件。i - 1也定位在交叉的左边。由于Ir-1位于最后两个交叉位点的左侧,并且已知交叉位点位于血清物质(Ss)位点的右侧,因此这些结果明确地将Ir-1定位在Ss位点和K区H-2抗原特异性之间。与GA和PLL基因的分布对比(9)。豚鼠对抗原的免疫反应是由PLL、GA和GT基因控制的,其特征是细胞免疫和特异性抗体的合成水平显著。缺乏这些基因的动物永远不会产生细胞免疫,在通常的免疫条件下也不会产生显著水平的抗体。因此,这些免疫反应基因的活性是应答动物和非应答动物之间明显的定性差异的原因,特别是在细胞免疫和载体功能方面。在豚鼠身上发现的遗传系统比在小鼠身上发现的遗传系统有一个明显的实验优势,即在自交系中发现的相同基因也在很大比例的随机繁殖的哈特利豚鼠身上发现(8,9)。控制GA、GT和PLL免疫反应的基因不是独立遗传的。正如预期的那样,GA基因和PLL基因在菌株2豚鼠中是相连的。大多数哈特利应答豚鼠对GA和PLL的反应也有联系。然而,有一小部分哈特利豚鼠对GA有反应而对PLL没有反应,或对PLL有反应而对GA没有反应。这些动物的存在可能是由于它们之间的交叉
H 2H-Ss Fig. 1. Diagram of the organization of the H-2 locus, with arrows indicating the ap-proximate position of crossovers resulting in recombinant H-2 alleles. The top arrows indicate a set of five reciprocal crossovers between H-2'and H-2b to give rise to H-2 and H-2'recombinant alleles. All five of these recombinant alleles localize Ir-l to the right of the crossover event. The three bottom arrows indicate a set of three reciprocal crossovers between H-2d and H-2k, giving rise to H-2a-Ssl, H-20-Ss', and H-2-Ssh. Once again, Ir-I is located to the right of these crossovers. H-2t-Ss' was derived from a crossover between H-2^-Ss' and H-2', and Ir-i is located to the left of this crossover. H-2'is derived from a crossover between H-2'and H-2q, and in this crossover event there was an outside marker (brachyury, T) which established that the crossover was a single crossover event. Ir-i was also localized to the left of this crossover. Since Ir-1 is to the left of the last two crossovers, and the crossovers are known to be to the right of the serum substance (Ss) locus, these results definitely localize Ir-I between the Ss locus and the K region H-2 antigenic specificities. trast with the distribution of the GA and PLL genes (9). The immune response of guinea pigs to the antigens, the recognition of which is under the control of the PLL, GA, and GT genes, is characterized by cellular immunity and the synthesis of significant levels of specific antibody. Animals lacking the genes never develop cellular immunity and do not produce significant levels of antibodies under usual conditions of immunization. The activity of these immune re-sponse genes is therefore responsible for clear-cut qualitative differences be-tween responder and nonresponder animals, particularly as concerns cellular immunity and carrier function. A signal experimental advantage that the genetic systems discovered in guinea pigs have over the ones identified in mice is the fact that the same genes detected in inbred strains are also found in a significant proportion of random-bred Hartley guinea pigs (8, 9). The genes controlling immune re-sponsiveness to GA, GT, and PLL are not inherited independently. As would be expected, the GA gene and the PLL gene are linked in strain-2 guinea pigs. Responsiveness to GA and PLL are also linked in most Hartley responder guinea pigs. However, there is a small proportion of Hartley guinea pigs that respond to GA but not to PLL or that respond to PLL but not to GA. The very existence of these animals that may result from a crossover between