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The experiments test the hypothesis that beta-adrenergic receptor is an independent unit that can be transferred from one adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4-6-1-1[ system to another. Turkey erythrocytes in which the catalytic activity of adenylate cyclase had been inactivated by N-ethylmaleimide or by heat contributed the beta-adrenergic receptor. Friend erythroleukemia cells (F cells) that possessed no measurable beta-adrenergic receptor contributed the adenylate cyclase. The erythrocytes in which the enzyme had been inactivated were fused with the F cells by Sendai virus. The cell ghosts of the fused preparation demonstrated adenylate cyclase activity which was strikingly enhanced by isoproterenol. Controls of fusion of F cells with each other or with human erythrocytes failed to show a response to isoproterenol. It was therefore concluded that the beta-adrenergic receptor of the turkey erythrocytes must have become functionally coupled to the adenylate cyclase of the mouse F cells. Activation by isoproterenol was demonstrable within a few minutes after fusion, and inhibitors of protein synthesis had no effect. Thus, coupling must have occurred between the preexisting components. The findings suggest that it may be possible in the future to confer on cells that possess an adenylate cyclase system new hormonal responses by inserting a receptor into their cell membrane. It is proposed that the procedure of massive heterologous cell fusion, as used in the present study, can be used to analyze the function of other cell membrane components.

One of the more recent associations of the murine H-2 major histocompatibility complex (MHC) with immune function has been the finding that cytotoxic T-effector cells generated by sensitization with viral-infected (1-6), chemically modified (7-9), or weak transplantation antigen-associated (10,11) syngeneic cells can efficiently lyse target cells which express the same viral, chemical, or weak antigenic agent, and which share the H-2K and/or H-2D regions of the MHC with the responding and/or stimulating cells. Furthermore, an additional contribution of a gene(s) within the H-2 complex has been demonstrated which controls immune response potential (Ir genes) in the generation of cytotoxic effector cells to trinitrophenyl (TNP)-modified self components (12,13). In such studies it was found that certain B10 congenic strains generated good cytotoxic responses to both TNP- modified H-2K and H-2D region products, whereas other B10 congenic strains exhibited preferential or exclusive reactivity against TNP-modified H-2K region products. Some of these recombinant strains differing in response potential to TNP- modified H-2D products expressed the same haplotype at the D end, but differed at the K end of H-2. The low responsiveness observed in the B10.A strain to TNP-modified H-2D(d) when compared to B10.D2 and (B10.A x B10.D2)F(1) for the same specificity, suggested a role of dominant Ir genes which map in K, I-A, I-B, I-J, and/or I-E (12, 14). In the present report an attemnpt was made to further map within the MHC the Ir gene(s) controlling cell-mediated lympholysis (CML) to TNP-modified H-2D(d), by using recombinant mouse strains on the A and B10 backgrounds. Irrespective of the genetic background, the s and k haplotypes at the K end generated high and low cytotoxic responses, respectively, to H-2D(d)-TNP. The intermediate responder and low responder status of the A.TL and A.AL strains, respectively, indicated that a gene mapping in the K region of H-2 influences response potential. Furthermore, the differences in the levels of cytotoxicity detected in the A.TH and A.TL strains suggested an additional I region influence. Taken together these findings raise the possibility that multiple genes mapping within different regions of the MHC control the level of T-cell-mediated cytotoxicity to chemically modified autologous cells.

Inactivation of alpha- and beta-thrombin by antithrombin-III and heparin was studied, since it had been suggested that two forms of thrombin exist with respect to heparin sensitivity (Machovich 1975b). It was found that the inactivation rates of alpha- and beta-thrombin by antithrombin were different, namely alpha-thrombin was more sensitive to antithrombin than beta-thrombin. Heparin facilitated the complex formation between alpha-thrombin and antithrombin-III, whereas beta-thrombin inactivation was only slightly affected. Furthermore, heparin protected alpha-thrombin against the inactivating effect of heat, while beta-thrombin lost its activity during the heat treatment. These findings suggest that the formation of beta-thrombin in blood circulation may have an important role in thrombosis predisposition.