Junji Yagi

EPITOPE-SPECIFIC REGULATION OF THE ANTIBODY RESPONSE AGAINST ALPHA-LACTALBUMINS IN THE MOUSE

The immune responsiveness to human and bovine alpha-lactalbumin (HuALA and BoALA) was found to be under the control of immune response (Ir) gene(s) linked to the major histocompatibility complex. H-2k mice responded to both HuALA and BoALA, whereas H-2d,s,and f mice respond only to HuALA; H-2b mice were nonresponders to both HuALA and BoALA. A survey with B10.A recombinant mouse strains enabled us to map the Ir gene in the I-A subregion. The responsiveness was shown to be dominant in F1 mice. The coimmunization of BoALA and HuALA resulted in the suppressed secondary antibody response to HuALA in B10.S (H-2s) and BALB/c (H-2d) but not in C3H (H-2k) suggesting that the low responsiveness against HuALA in these strains is due to an active suppression. The transfer of splenic T cells of B10.S mice primed with BoALA into syngeneic animals suppressed the response to HuALA. T cells specific for a particular epitope present on BoALA appeared to suppress the immune response to other epitopes on HuALA. Thus, the presence of epitope-specific suppressor T cells seems to account for this Ir-gene-controlled low responsiveness to ALA in H-2s mice.

Adaptive Construction of the Immune Circuit

Monoclonal antibodies (mAb) against I region-controlled epitopes expressed exclusively on mature functional T cells but not on B cells and macrophages (anti-Iat and anti-I-J) were found to inhibit class II MHC-restricted cell interactions in the immunological circuit. We have studied phenotypic changes of the MHC restriction site by the use of these mAb in various types of radiation bone marrow chimeras and found that these epitopes undergo systematic alterations according to the environmental MHC. Both I-J and Iat epitopes were found to be associated with the surface structure transmitting the activation signals by the fact that mAb can induce proliferation of unprimed T cells via the induction of IL-2 receptors. T cell clones expressing these epitopes were able to induce a regulatory T cell that recognizes the initial epitopes and suppressor augments the response of T cells having the same epitopes. These results indicate that Iat and I-J epitopes are associated with the inducible T cell receptors for self with which the immunological circuit is constructed.

Epitope Organizations of I Region Products Associated with Antigen-Specific Augmenting and Suppressor T Cell Factors

We have reported previously two distinct antigen specific T cell factors having the ability to augment (TaF) or to suppress (TsF) the in vitro secondary antibody response (1). Subsequently, several T cell hybridomas producing these factors have been established and maintained in our laboratory (2,3). TaF and TsF produced by these hybridomas had identical functional properties to those from normal antigen-primed T cells. Previous studies revealed a two-chain structure of these soluble products: one chain possesses antigen-binding ability and the other bears determinants encoded by the major histocompatibility complex (MHC); I-A subregion gene product for TaF and I-J subregion gene product for TsF. Both these determinants have been found to be different from conventional class II Ia antigens.