Molecular Identification and Immunological Significance of I-J Molecule.

I-J has been an enigmatic molecule on T cells which undergoes a systematic somatic alteration according to the environmental major histocomcompatiManagement complex （MHC） During their ontogeny of T cells as demonstrated in radiation bone marrow chimeras and class II gene transgenic mice。因此， I-J并不是MHC基因的直接产物，但它是一种适应性分子对自身MHC多态性最可能成为一种受体样的分子。为了研究I-J的分子性质，我们已经建立了一个系列的IL-2依赖T细胞克隆体，其中包括不同的单倍体起源，包括辐射骨骼marrow chimeras。它们都是具有不同MHC限制特性的助手（Th）或抑制剂（Ts）克隆人。They are mostly CD4^+ Th and Ts clones except for a few CD8^+ Ts clones。Ts亚型是由其生产IL-2和IL-4的能力定义的，缺乏B细胞的辅助活性，以及其对MHC-垫抗体反应的强抑制剂活性 ... More ched T and B cells.Many of the H-2 ^k-restricted clones were found to be positive for the staining with a monoclonal anti-I-J ^K. Both I-A^k-and I-E^k-restricted clones derived from different？ins including H-2 ^b-> H-2 ^k chimeras expressed the same I-J^k epitope。I-J分子不与TcR/CD 3复合体协同调制，通过对这些T细胞克隆体的一个或两个维度凝胶进行免疫吸收和亚序列分析，发现I-J分子是一种新颖的二聚表面分子，由86，000 MW 83，000个葡聚糖基亚组成的来自TcR异聚物、MHC II类抗原和先前已知的T细胞的二聚蛋白质。一种单体形式也存在于一些T细胞克隆体上。蛋白质测序和基因克隆方法目前正在进行中，I-J多态性似乎在T细胞抗原识别后早期信号转换的规则中扮演了一个重要的角色。当T细胞克隆用I-J^k epitope预处理时，单克隆反I-J ^k，Ca^<++>影响被一个亚序刺激诱导用抗脉冲抗呈现的细胞被严重抑制。Ca^<++>响应受反TcR heterodimer但不受反CD 3或Con A类似于反I-J. I-J分子的连接是由intact抗体引起的，但不是由Fab引起的，这是一种抑制的初始化。Ca^<++>抑制的模式与T克隆人预先孵化的T克隆人非常相似。这些结果表明，I-J受体中的负信号可能会抑制自身MHC-反应性T细胞中的两个在本体和周期中。Less（低）

I-J has been an enigmatic molecule on T cells which undergoes a systematic somatic alteration according to the environmental major histocompatibility complex (MHC) during their ontogeny of T cells as demonstrated in radiation bone marrow chimeras and class II gene transgenic mice. Thus, I-J is not a direct product of an MHC gene as originally thought, but is an adaptive molecule to a self MHC polymorphism most likely to be a receptor-like molecule for self. In order to study the molecular nature of I-J, we have established a series of IL-2 dependent T cell clones from different haplotype origins including radiation bone marrow chimeras. They are either helper (Th) or suppressor (Ts) clones with different MHC restriction specificities. They are mostly CD4^+ Th and Ts clones except for a few CD8^+ Ts clones. Ts subtype was defined by its inability to produce both IL-2 and IL-4, lack of helper activity for B cells, and by its strong inhibitory activity for the antibody response of MHC-mat … More ched T and B cells.Many of the H-2^k-restricted clones were found to be positive for the staining with a monoclonal anti-I-J^K. Both I-A^k- and I-E^k- restricted clones derived from different origins including H-2^b- > H-2^k chimeras expressed the same I-J^k epitope. The I-J molecule was not co-modulated with TcR/CD3 complex.By immunoprecipitation and subsequent one- or two-dimensional gel analyses of the lysate of these T cell clones, I-J molecule was found to be a novel dimeric surface molecule of MW 86,000 composed of 43,000 glycopeptide subunits differing from TcR heterodimer, MHC class II antigen, and previously known dimeric proteins of T cells. A monomeric form also existed on some T cell clones. Protein sequencing and gene cloning approaches are now under way.The I-J polypeptide seems to play an important role in the regulation of early signal transduction in T cells after antigen-recognition. When T cell clones with the I-J^k epitope was pretreated with the monoclonal anti-I-J^k, the Ca^<++> influx induced by a subsequent stimulation with antigen-pulsed antigen-presenting cell was greatly inhibited. The Ca^<++> response induced by anti-TcR heterodimer but not by anti-CD3 or Con A was similarly inhibited by the anti-IーJ. The ligation of I-J molecules by intact antibody but not by Fab was required for the initiation of suppression. The pattern of inhibition of Ca^<++> influx was very similar to that observed in Th clones preincubated with Ts clones. These results indicate that the negative signal from I-J receptor may inhibit the expansion of self MHC-reactive T cells both in ontogeny and in periphery. Less