Using BALB/c and CBA/J mice, the Iregion associated (Ta) binding capacity and T-cell immunogenicity of a panel of 14 overlapping peptides that span the entire sequence of the protein staphylococcal nuclease (Nase) was examined to evaluate major histocompatibility gene complex (MHC) control of T-cell responses. Ta binding and Ia-restricted T-cell immunogenicity could be determined for a total of 54 peptide-MHC combinations. Only 30% of the 54 instances examined involved detectable la binding, but they represented almost all (12 of 13) of the immune responses found. However, binding to Ia was not sufficient to ensure T-cell immunogenicity, since only 70% of the binding events were productive-i.e., were associated with an immune response. Thus, Ta molecules have the expected characteristics of a highly permissive capacity for antigen interaction that allows them to function as restriction elements for a large universe of antigens. On the other hand, since the Ta molecules cannot distinguish between self and non-self, not all antigen-Ta interactions would be permitted to elicit a T-cell response. It appears that both Ta

Growth factor activity has been identified in the chondrocytes and extracellular matrix (ECM) fractions of human costal cartilage. There was about five times more growth factor activity in the ECM than was found to be associated with the chondrocytes. The growth factor activity in chondrocytes was found to be associated with chromatin. Both the chromatin-associated growth factor (CAGF) activity and extracellular matrix growth factor (EMGF) activity were characterized for molecular weight, charge, and the effect of reduction by sulfhydryl reducing reagents. Biorex cation exchange chromatography showed that both CAGF and EMGF were cationic. CAGF and EMGF have molecular weights between 15,000 and 18,000 as determined by size exclusion chromatography on HPLC TSK 3000 columns equilibrated with guanidine-HCl and dithiothreitol.

We have examined the requirements for the activation of normal T cells by two anti-T cell receptor antibody preparations, including a rabbit antiserum, R3497, which binds to all normal T cells, and a rat monoclonal antibody, KJ16-133, which binds to about 20% of T cells. The requirements for stimulation of T cells by both antibodies were similar. Soluble antibodies in the absence of accessory cells (AC) failed to induce either proliferation or the expression of IL 2 receptors, and the addition of either IL 2 or PMA failed to synergize with these soluble antibodies for an AC-independent proliferative response. Activation could only be achieved in the presence of Fc receptor-positive AC, although Fc receptor expression alone appeared not to be sufficient for AC activity because some Fc receptor-positive cells did not function in this capacity. Activation with anti-receptor antibody conjugated to Sepharose 4B beads could be demonstrated in the presence of some exogenous cofactors, such as IL 2 and PMA, but not in the presence of recombinant IL 1. When activation by soluble antibody plus AC was compared to activation by bead-conjugated antibody + recombinant IL 2, it was found that the former favored the stimulation of Lyt-2+ cells. The effects of the addition of anti-L3T4 monoclonal antibody was also examined in this system. Anti-L3T4 inhibited the response of L3T4+ cells when used in the presence of Ia+ as well as Ia- AC, and it also inhibited activation in a system in which KJ16-133 conjugated to Sepharose was used in the absence of AC. Because anti-L3T4 had an inhibitory effect in the presence of Ia- AC as well as in the absence of any AC, it is concluded that L3T4 does not necessarily function by interacting with Ia on the surface of AC, and may directly transmit down-regulatory signals when bound by anti-L3T4.

The immune response to the chemically defined DNP-oligo-L-lysine antigens is under Ir gene control in the guinea pig. Strain 2 (responder) guinea pigs mount a highly specific T cell-mediated and humoral immune response capable of discriminating closely related DNP-peptides. In contrast, strain 13 (nonresponder) animals fail to mount a cell-mediated response, and produce antibody that is only DNP-specific. In these studies a common idiotypic determinant is defined on highly specific anti-epsilon,DNP-Lys10 antibody produced by strain 2 guinea pigs. Ir gene nonresponder antibody is idiotype-negative. The presence of the idiotypic determinant distinguishes responder anti-epsilon,DNP-Lys10 antibody from responder antibodies elicited by structurally related antigens such as epsilon,DNP-Lys9 and alpha,DNP-Lys10-. Investigation of the regulation of idiotype expression demonstrated that production of idiotype-positive antibody requires the presence of viable, antigen-responsive T cells. Moreover, genetic analysis revealed that expression of the shared idiotype correlates directly with the phenotypic expression of I region genes (DTH responsiveness, Ia antigens) in (2 x 13)F1 x 13 backcross and randomly bred Hartley guinea pigs. Thus, Ir gene regulation of the immune response may be reflected in the v region specificities expressed by antigen-specific B cell clones.