I–J as an idiotype of the recognition component of antigen-specific suppressor T-cell factor

Abstract

The I–J determinant of membrane glycoprotein is known to be expressed exclusively on suppressor T cells (Ts), which have a crucial role in the regulation of immune responses¹. I–J also comprises part of the soluble factor (TsF) with suppressor activity which is secreted from Ts. Gene-mapping experiments have indicated that the I–J gene lies between the I–A and I–E subregions of the mouse major histocompatibility complex (MHC)^2,3 and is defined by the H–2 congeneic pair, that is, B10.A(3R) and B10.A(5R)⁴. In fact, antibodies raised in the reciprocal combinations of B10.A(3R) and B10.A(5R) define the I–J^b and I–J^k alleles, and are able to detect the I–J determinants on Ts and TsF. Biochemical and functional analyses^5–10, using I–J-positive Ts clones and hybridomas, have demonstrated that monoclonal anti-I–J antibodies precipitate I–J^k or I–J^b with a relative molecular mass of 25,000–28,000 (25–28K) and that the I–J⁺ molecule mediates the restriction specificity of TsF in. association with an antigen-binding protein (45K). However, molecular genetic studies on the I–J gene^11–13 reveal no genetic difference between B10.A(3R) and B10.A(5R) and also that there is no room to accommodate a gene encoding I–J in the expected I region. These discrepancies between the molecular genetic and serological/functional data require explanation. Here we demonstrate that Ts and TsF expressing I–J of the host type were produced by fully allogeneic bone marrow cells of donor origin in chimaeric mice, when the chimaeras received the host antigen-presenting cells (APC) at the time of immunization. The results show that APC are necessary for the activation and clonal expansion of Ts and also support the notion that I–J is an idiotypic determinant of the recognition component of Ts and TsF.