Molecular Identification and Immunological Significance of I-J Molecule.

I-J has been an enigmatic molecule on T cells which undergoes a systematic somatic alterationaccording to the environmental major histocompatibility complex (MHC) during their ontogeny of Tcells as demonstrated in radiation bone marrow chimeras and class II gene transgenic mice. Thus，I-J不是一个直接产品，一个MHC gene as originally thought，but is an adaptive molecule to a self MHC polymorphism most likely to be a receptor-like moleculefor self. In order to study the molecular nature of I-J，我们已经established a series of IL-2 dependent T cell clones from different haplotype origins包含radiation bone marrow chimeras.他们都是helper （Th）或suppressor (Ts) clones withdifferent MHC restriction specificities. They are mostly CD4^+ Th and Ts clones except for a fewCD8 + 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 thestaining with a monoclonal anti-I-J K. Both I-A^ K - and I-E^ K - restricted clones derived fromdifferent origins including H-2^b- > H-2^k chimeras expressed the same I-J^k epitope. the I-Jmolecule not co-modulated with TcR/CD3 complex.By immunoprecipitation and subsequent one- ortwo-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 43,000glycopeptide subunits differing from TcR heterodimer, MHC class II antigen，以前已知的dimeric proteins of T cells. A monomeric form also existed on some T cellclones. Protein sequencing and gene cloning approaches are now under way.The I-J polypeptide seemsto play an important role in the regulation of early signal transduction in T cells afterantigene -recognition. When T cell clones with the I-J^k epitope was pretreated with the monoclonalanti - i - j ^ k,the Ca influx induced by a subsequent stimulation with antigen-pulsed antigen-presenting cellwas greatly inhibited. The Ca <++> response induced by anti-TcR heterodimer but not by anti-CD3 orCon A was similarly inhibited by the anti-I -J . the ligation of I-J molecules by intact antibody butFab was required for the initiation of suppression. the pattern of inhibition of Ca <++>influx very similar to observed in Th clones preincubated with Ts clones.这些影响indicate that the negative signal from I-J receptor may inhibit the expansion of self MHC-reactive Tcells both in ontogeny and in periphery. Less

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