Abstract
The magnitude of the immune response of lymphocytes to defined antigenic determinants of ungulate insulins is controlled by the products of H-2 genes. Based on the crystallographically solved structure of porcine insulin, the close homology of all the ungulate insulins, and the amino acid substitutions, we built models of the different insulins. We analyzed the likely conformations of the antigenic determinants, and proposed structural specificities accounting for the immunologic phenomena observed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amzel, L. M., Polyak, R. J., Saul, F., Varga, J. M., and Richards, F. F.: The three-dimensional structure of a combining region-ligand complex of immunoglobulin NEW at 3.5 Å resolution. Proc. Natl. Acad. Sci. U.S.A. 71: 1427–1430, 1974
Atassi, M. Z.: The antigenic structure of myoglobin and initial consequences of its precise determination. CRC Cit. Rev. Biochem. 6: 337–369, 1979a
Atassi, M. Z.: Determination of the entire antigenic structure of native lysozyme by surface-stimulation synthesis, a novel concept in molecular recognition. CRC Crit. Rev. Biochem. 6: 371–400, 1979b
Bentley, A., Dodson, G., Hodgkin, D., and Mercola, D.: Structure of insulin in 4-zinc insulin. Nature 261: 166–168, 1976
Binz, H. and Wigzell, H.: Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T cell receptors with specificity for the same alloantigens. J. Exp. Med. 142: 197–211, 1975
Cohen, I. R. and Talmon, J.: H-2 genetic control of the response of T lymphocytes to insulins priming of nonresponder mice by forbidden variants of specific antigenic determinants. Eur. J. Immunol. 10: 284–289, 1980
Cohen, I. R., Talmon, J., Lev-Ram, Y., and Ben-Nun, A.: Immune response genes have a variable influence on the selection of antigenic foreign and self determinants of insulin. Proc. Natl. Acad. Sci. U.S.A. 76: 4066–4070, 1979
Davies, D. R., Padlan, E. A., and Segal, D. M.: Three dimensional structure of immunoglobulins. Annu. Rev. Biochem. 44: 639–667, 1975
De Meyts, P., van Obberghen, E., Roth, J., Wellmer, A., and Brandenburg, D.: Mapping of the residues responsible for the negative cooperativity of the receptor binding region of insulin. Nature 273: 504–509, 1978
Dodson, F., Dodson, G., Hodgkin, D. C., and Reynold, C. D.: Structural relationship in the two-zinc insulin hexamer. J. Biochem. 57: 469–479, 1979
Eichman, K. and Rajewsky, K.: Induction of T and B cell immunity by anti-idiotypic antibody. Eur. J. Immunol. 5: 661–666, 1975
Ely, K. R., Girlins, R. I., Schiffer, M., Cunningham, D. E., and Edmonson, A. B.: Preparation and properties of crystals of a Bence-Jones dimer with mercury inserted into the interchain disulfid bond. Biochem. 12: 4233–4237, 1973
Freidman, A., Gitler, C., and Cohen, I. R.: Molecular aspects of the processing and presentation of avidin by macrophages to T lymphocytes. In C. W. Pierce, S. E. Cullen, J. Kapp, B. D. Schwartz, and D. C. Shreffler (eds.): Ir Genes: Past, Present and Future, in press, Humana Press, Clifton, N. J., 1983
Givol, D., Gavish, M., Zakut, R., Ben-Neriah, Y., and Lonai,P.: Combining site and antigenic determinants of the V region. Hematologia Budap. 12: (1-4): 15–24, 1979
Grossman, Z. and Cohen, I. R.: A theoretical analysis of the phenotypic expression of immune response genes. Eur. J. Immunol. 10: 633–640, 1980
Ishii, N., Baxevanis, C. N., Nagy, Z. A., and Klein, J.: Responder T cells depleted of alloreactive cells respond to antigen presented on allogeneic macrophage from nonresponder strains. J. Exp. Med. 154: 978–982, 1981
Keck, K.: Ir-gene control of immunogenicity of insulin and A chain loop as a carrier determinant. Nature 254: 78–79, 1975
Nyburg, S.C.: Some use of best-molecular fit routine. Acta Crystalograph. Sect. B. 30: 251–253, 1974
Ranghino, G., Talmon, J., Yonath, A., and Cohen, I. R.: The conformation of antigenic determinants of insulin and H-2 genes control of the immune response of T lymphocytes. In M. Balaban, L. J. Sussman, W. Traub, and A. Yonath (eds.): Structural Aspects of Recognition and Assembly in Biological Macromolecules, pp. 263–279, Balaban International Science Services, Rehovot, Philadelphia, 1981
Richards, F. M. and Richmond, J.: Solvents, interfaces and protein structure. Ciba Found. Symp. 60, 23–45, 1978
Rosenwasser, L. J., Barcinski, M. A., Schwartz, R. H., and Rosenthal, A. S.: Immune response gene control of determined selection. II. Genetic control of the murine T lymphocyte proliferative response to insulin. J. Immunol. 123: 471–476, 1979
Schiffer, M., Girlins, R. L., and Ely, K. P.: Structure of type Bence-Jones protein at 3.5 Å resolution. Biochemistry 12: 4620–4631, 1973
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Talmon, J., Ranghino, G., Yonath, A. et al. Structural analysis of insulin determinants seen by T cells directed by H-2 genes. Immunogenetics 18, 79–89 (1983). https://doi.org/10.1007/BF00401358
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00401358