The I-J glycoprotein: genetic control, biochemistry, and function.

The I-J molecule is a mannosylated protein expressed early in T cell ontogeny in partially shielded form, later fully exposed on an activated T cell subset. Others determined a 25-30,000 molecular weight for cellular (Kumagai et al. 1984) and secreted forms (Taniguchi et al. 1984). Both the cell membrane and secreted types seem to govern genetically-restricted interactions completing suppressor cell circuits. The soluble I-J polypeptide has no antigen-binding site, but associates with an antigen-binding chain via disulfide bonding (Taniguchi et al. 1984, Lei et al. 1983). Similarly, evidence suggests that cellular I-J molecules are part of or proximal to T cell antigen receptor complexes (Fig. 4). At least two genes control T cell I-Jk expression, one apparently in I-E, another on chromosome 4. Undiscovered loci may also participate. Since I-J+ T cells do not transcribe I-region DNA, the I-E gene must be an untranscribed regulatory element in T cells or a protein translated in the host environment. If in the host environment, it probably does not function enzymatically to form T cell I-J epitopes; removed from the host, T cells biosynthesize complete I-J determinants. Host I-E gene products may regulate I-J expression in an early T cell maturation step. For example, the E alpha E beta proteins of thymic macrophages and epithelial cells may drive the expansion of T cells with E alpha E beta-complementary receptors encoded by I-J genes outside H-2. Genetic control of this self receptor would then apparently map to the selective ligand gene, I-E, as well as the I-J structural gene elsewhere (Klyczek et al. 1984b). This attractive theory, proposed in its original form by Jerne (1971) and later by Schrader (1979), has received significant support. Definitive proof must await further experimentation.