Abstract
The differences between the immune response (Ir) phenotypes ofH-2 gene-controlled high- and low-responder mice have been attributed to events occurring at the interaction between antigen-presenting cells (APC) and lymphocytes. To investigate this interaction we undertook a study of molecular events in the processing of avidin, a molecule whose uniquely strong affinity for binding to biotin renders it traceable at very low concentrations, and a molecule to which the T-lymphocyte immune response is controlled byIr genes. In this paper we describe the generation of processed avidin by APC and characterize it biochemically and,immunologically. We found that APC ofH-2 genetically high-and low-responder mice were indistinguishable in their capacity to generate immunogenic processed avidin (PA). Immunogenic PA differed from native avidin in size and carbohydrate moieties, but preserved its capacity to bind biotin, and was 1000-fold more efficient than NA as an immunogen for primed T lymphocytes. Primed T lymphocytes appeard to recognize PA that was conformationally intact. Highly immunogenic PA was notH-2 restricted. Thus, differences in the Ir phenotype of the response to avidin could not be attributed to determinant selection by APC.
Similar content being viewed by others
Abbreviations
- APC:
-
antigen-presenting cells
- BSA:
-
bovine serum albumin
- Con a:
-
concanavalin A
- Ir:
-
immune response
- NA:
-
native avidin
- NMS:
-
normal mouse serum
- PA:
-
processed avidin
- PEC:
-
peritoneal exudate cells
- PNA:
-
peanut agglutinin
- SBA:
-
soybean agglutinin
- WGA:
-
wheat germ agglutinin
References
Bayer, E. A. and Wilchek, M.: The use of the avidin-biotin complex as a tool in molecular biology.In D. Glick (ed.):Methods of Biochemical Analysis, Vol. 26, pp. 1–45, John Wiley & Sons, New York, 1980
Bayer, E.A., Wilchek, M., and Skutelsky, E.: Affinity cytochemistry: The localization of lectin and antibody receptors on erythrocytes via the avidin-biotin complex.FEBS Lett 68: 240–244, 1976
Benacerraf, B.: A hypothesis to relate the specificity of T lymphocytes and the activity of I region specific Ir genes in macrophages and B lymphocytes.J. Immunol. 120: 1809–1812, 1978
Benacerraf, B. and Germain, R. N.: The immune response genes of the major histocompatibility complex.Immunol. Rev. 38: 70–119, 1978
Bolton, A. E. and Hunter, W. M.: The labeling of proteins to high-specific radioactivities by conjugation to a125I-containing acylating agent. Application to the radioimmunoassay.Biochem. J. 133: 529–539, 1973
Clark, R. B. and Shevach, E. M.: Generation of T cell colonies from responder strain 2 guinea pigs that recognize the copolymer L-glutamic acid, L-lysine in association with nonresponder strain 13 Ia antigens.J. Exp. Med. 155: 635–640, 1982
Cohen, I. R. and Talmon, J.: H-2 genetic control of the response of T lymphocytes to insulin. 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, V., and Ben-Nun, A.: Immune response genes have a variable effect on the selection of antigenic foreign and self determinants of insulin.Proc. Natl. Acad. Sci. USA 76: 4066–4070, 1979
Cowing, C., Pincus, S. H., Sachs, D. H., and Dickler, H. B.: A subpopulation of adherent accessory cells bearing both I-A and I-E or C-subregion antigens is required for antigen specific murine T lymphocyte proliferation.J. Immunol. 121: 1680–1686, 1978
Ellner, J. J., Lipsky, P. E., and Rosenthal, A. S.: Antigen handling by guinea pig macrophages: Further evidence for the sequestration of antigen relevant for activation of primed T lymphocytes.J. Immunol. 118: 2053–2057, 1977
Erb, P., Feldman, M., and Hogg, N.: Role of macrophages in the generation of helper T cells. II. Nature of genetically related factor derived from macrophages incubated with soluble antigens.Eur. J. Immunol. 6: 365–372, 1976
Farr, A. G., Keily, J. M., and Unanue, E. R.: Macrophage-T cell interactions involvingListeria monocytogenes. Roles of the H-2 gene complex.J. Immunol. 122: 2395–2404, 1979
Friedman, A. and Cohen, I. R.: Molecular events in the processing of aviden by antigen-presenting cells (APC). I. The immune response of T lymphocytes to aviden is regulated byH-2-linkedIr genes.Immunogenetics 18: 267–275, 1983
Friedman, A., Zerubavel, R., Gitler, C., and Cohen, I. R.: Molecular events in the processing of avidin by antigen-presenting cells (APC). III. Activation of T-lymphocyte lines andH-2 restriction are mediated by processed avidin associated withI-region gene product.Immunogenetics 291–302, 1983
Germain, R. N.: Accessory cell stimulation of T cell proliferation requires active antigen processing, Ia restricted antigen presentation and a separate nonspecific second signal.J. Immunol. 127: 1964–1966, 1981
Gordon, S., Unkeless, J., and Cohn, Z. A.: Induction of macrophage plasminogen activator by endotoxin stimulation and phagocytosis. Evidence for a two stage process.J. Exp. Med. 140: 995–1010, 1974
Green, M.: Avidin.Adv. Protein Chem. 29: 85–133, 1975
Howie, S. and McBride, W. H.: Cellular interactions in thymus-dependent antibody responses.Immunol. Today 3: 273–278, 1982
Ishii, N., Baxevanis, C. N., Nagy, Z. A., and Klein, J.: Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains.J. Exp. Med. 154: 978–982, 1981
Karnovsky, M. L., Lazdins, J., Drath, D., and Harper, A.: Biochemical characteristics of activated macrophages.Ann. N. Y. Acad. Sci. 256: 266–274, 1975
Lee, K-C., Singh, B., Barton, M. A., Procyshyn, A., and Wong, M.: A simple reliable system for studying antigen specific murine T cell proliferation.J. Immunol. Methods 25: 159–170, 1979
Lonai, P., Steinman, L., Friedman, V., Drizlikh, G., and Puri, J.: Specificity of antigen binding by T cells: Competition between soluble and la-associated antigens.Eur. J. Immunol. 11: 382–387, 1981
Matzinger, P.: A one receptor view of T cell behaviour.Nature 292: 497–501, 1981
Mishell, B. B. and Stiigi, S. M. (eds.):Selected Methods in Cellular Immunology, W. H. Freeman and Co., San Francisco, 1980
Morahan, P. G.: Macrophage nomenclature: Where are we going?J. Reticuloendothel. Soc. 27: 223–235, 1980
Nagy, Z. A. and Klein, J.: Macrophage or T cell, that is the question.Immnunol. Today 2: 288–289, 1981
Nathan, C. F. and Terry, W. D.: Decreased phagocytosis by peritoneal macrophages from BCG treated mice.Cell Immnunol. 23: 295–304, 1977
Niederhuber, J. E.: The role of I region gene products in macrophage-T lymphocyte interactions.Immnunol. Rev. 40: 28–52, 1978
Rosenthal, A. S.: Determinant selection and macrophage function in genetic control of immune responses.Immnunol. Rev. 40: 135–152, 1978
Rosenthal, A. S.: Determinant selection and macrophage function.Immnunol. Today 3: 33–34, 1982
Rosenthal, A. S., Barcinski, M. A., and Blake, J. T.: Determinant selection is a macrophage dependent immune response gene function.Nature 267: 156–158, 1977
Rosenthal, A. S., Barcinski, M. A., and Rosenwasser, L. J.: Function of macrophages in genetic control of immune responsiveness.Fed. Proc. 37: 79–85, 1978
Schwartz, R. H.: A clonal deletion model for Ir gene control of the immune response.Scand. J. Immnunol. 7: 3–10, 1978
Schwartz, R. H., Jackson, L., and Paul, W. E.: T lymphocyte enriched murine peritoneal exudate cells. I. A reliable assay for antigeninduced T lymphocyte proliferation.J. Immunol. 45: 1330–1338, 1975
Schwartz, R. H., Yano, A., and Paul, W. E.: Interaction between antigen-presenting cells and primed T lymphocytes. An assessment for Ir gene expression in the antigen presenting cell.Immunol. Rev. 40: 153–180, 1978
Schwartz, R. H., Yano, A., Stimpfling, J. H., and Paul, W. E.: Gene complementation in the T lymphocyte proliferative response to GLØ: A demonstration that both immune response genes must be expressed in the same antigen presenting cell.J. Exp. Med. 149: 40–57, 1979
Seta, M.: Antigenicity: Some molecular aspects.Science 166: 1365–1374, 1969
Skutetsky, E. and Bayer, E. A.: The ultrastructural localization of cell surface glycoconjugates: Affinity cytochemistry via the avidin-biotin complex.Biol. Cell. 36: 237–252, 1979
Snedcore, G. W. and Cochran, W. G.:Statistical Methods, The Iowa State University Press, Ames, Iowa, 1967
Steinman, R. M., Chen, L. L., Witman, N. D., Nussenzweig, M. C., Adams, J. C., and Cohn, Z. A.: Dendritic cells and macrophages: Current knowledge of their distinctive properties and functions.In R. Van-Furth (ed.): Mononuclear Phagocytes, III, pp. 1781–1802, Martinus Nijhoff, N. V., The Hague, 1980
Unanue, E. R.: The regulation of lymphocyte functions by the macrophage.Immnunol. Rev. 40: 227–255, 1978
Unanue, E. R.: The regulatory role of macrophages in antigen stimulation, Part two. Symbiotic relationship between lymphocytes and macrophages.Adv. Immunol. 31: 1–136, 1981
Ziegler, K. and Unanue, E. R.: Identification of a macrophage antigen-processing event required for I region-restricted antigen presentation to T lymphocytes.J. Immnunol. 127: 1869–1875, 1981
Ziegler, K. and Unanue, E. R.: Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells.Proc. Natl. Acad. Sci. USA 79: 175–178, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Friedman, A., Zerubavelt, R., Gitler, C. et al. Molecular events in the processing of avidin by antigen-presenting cells (APC). Immunogenetics 18, 277–290 (1983). https://doi.org/10.1007/BF00952966
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00952966