1326 I - J - Related Antigen Presentation

Regulat ion of the immune system has been shown (1) to result from complex interactions among subsets of lymphocytes and other cells. Some of these interactions are defined as genetically restricted when the effective interaction requires a certain identity among the cells involved. The genetic restrictions reflect the specificity of the T lymphocyte 's receptors and are of two types: (a) As originally proposed by Jerne, idiotype specificities determined by Igh-linked genes direct interactions among lymphocyte clones, including T lymphocytes. (b) The other set of restrictions concerns the antigens of the major histocompatibil i ty complex (MHC), 1 H-2 in the mouse. Ly-1 + helper and delayed-type hypersensitivity T cells (DTH) are restricted to react to antigen together with gene products of the I-A or I-A-I-E subregions of the murine H2 complex, whereas cytolytic T cells are commit ted to interact with K and D specificities. In this study, we analyzed the genetic restrictions controll ing the interactions of suppressor T cell subsets. Suppressor cell circuits in the regulation of T cell dependent antigen-specific D T H have been well studied in several murine systems (2-7). In the sequence of activation of the three major subsets of suppressor T cells (Tsl, Ts2, Ts3), the interaction between second-order suppressor cells (Ts2) and third-order suppressor cells (Ts3) has been shown to be restricted by genes that map to the X I I t h (Igh1 linked) and X V I I t h (H-2 MHC) chromosomes (3, 6) of the mouse. The structural elements for Igh-1linked restriction appear to be clonally expressed, idiotypic determinants present on the ant igen-binding cell surface receptors of first-order suppressor cells (Tsl) and also identifiable on soluble suppressor factor produced by Tsl (TsF1) (5). The same or similar idiotype determinants are present on the cell surface receptors of the Ts3 cell (7). It has been shown that Ts l or TsF1 stimulates a populat ion of anti-idiotypic Ts2 cells capable of producing and secreting TsF2. TsF2 binds to and triggers Ts3 cells that express the same kind of idiotypic determinants that are on the TsF1 molecule. This idiotypy, therefore, appears to govern certain aspects of Ts subset interactions. On the other hand, a l though many suppressor T cells express I-J determinants, and I-J restrictions have been reported, little is known about how such a restriction occurs