1990 Fiscal Year Final Research Report Summary
Molecular Identification and Immunological Significance of I-J Molecule.
Grant-in-Aid for General Scientific Research (A)
|Allocation Type||Single-year Grants |
|Research Institution||University of Tokyo |
TADA Tomio University of Tokyo, professor, 医学部・医学科, 教授 (10009136)
SEIKI Makoto University of Tokyo, Associate Professor, 医学部・医学科, 助手 (50226619)
SANO Kunio University of Tokyo, Associate Professor, 医学部・医学科, 助手 (20192601)
KARASUYAMA Hajime University of Tokyo, Associate Professor, 医学部・医学科, 助手 (60195013)
|Project Period (FY)
1989 – 1990
|Keywords||I-J / Major histocompatibility complex / Suppressor T cell / Helper T cell / Ca^<2+> influx / Signal transduction|
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
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
Research Products (26results)