Abstract
We investigated the interaction between processed avidin (PA) and avidin-specific lines of T lymphocytes free of resident antigen-presenting cells (APC). We found that PA was able to replace the requirement for APC in the T-lymphocyte proliferative assay, only if the PA was associated with an Ia-positive moiety (IPM) supplied by the APC. In addition to supplying a necessary signal for a proliferative response to PA, IPM imposedH-2 restriction on the PA molecule. The association between PA and IPM was reversible and the two moieties could be physically separated and recombined. The results support a conclusion that major histocompatibility restriction of the interaction between T lymphocytes and APC is due to the association between processed antigen and an APC element containing I-region products.
Similar content being viewed by others
Abbreviations
- APC:
-
antigen-presenting cells
- Ir:
-
genes immune-response genes
- PA:
-
processed avidin
- NA:
-
native avidin
- LNC:
-
lymph-node cells
- BSA:
-
bovine serum albumin
- PPD:
-
purified protein derivative
- CS:
-
control supernatant
- PBSA:
-
processed BSA
- IPM:
-
Ia-positive moiety
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
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. V.: The immune response genes of the major histocompatibility complex.Immunol. Rev. 38: 70–119, 1978
Ben-Nun, A. and Cohen, I. R.: Experimental autoimmune encephalomyelitis (EAE) mediated by T-cell lines: Process of selection of lines and characterization of cells.J. Immunol. 129: 303–309, 1982
Clark, R. B. and Shevach, E. M.: Generation of T cell colonies from responder strain 2 guinea pigs that recognize the copolymer L-glutamine acid, L-lysine in association with nonresponder strain 13 la 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 insulins. Priming of nonresponder mice by forbidden variants of specific antigenic determinants.Ear. 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 antigen foreign and self determinants of insulin.Proc. Natl. Acad. Sci. U.S.A. 76: 4066–4070, 1979
Erb, P. and Feldman, M.: The role of macrophages in the generation of T helper cells. III. Influence of macrophage derived factors in helper cell induction.Eur. J. Immunol. 5: 759–766, 1975
Erb, P., Feldman, M., and Hogg, N.: The role of macrophages in the generation of T helper cells. IV. Nature of genetically related factor derived from macrophages incubated with soluble antigens.Eur. J. Immunol. 6: 365–372, 1976
Eshhar, Z., Strassman, G., Waks, T., and Mozes, E.: In vitro and in vivo effector cells mediating DTH responses to a protein and synthetic polypeptide antigen.Cell Immunol. 47: 378–389, 1979
Friedman, A. and Cohen, I. R.: Molecular events in the processing of avidin by antigen-presenting cells (APC). I. The immune response of T lymphocytes to avidin is regulated byH-2-LinkedIr genes.Immunogenetics 18: 267–275, 1983
Friedman, A., Gitler, C., and Cohen, I. R.: Molecular aspects of the processing and presentation of avidin by macrophages to T lymphocytes.In C. W. Pirece, S. E. Cullen, J. A. Kapp, B. D. Schwartz, and D. C. Shreffler (eds.):Ir Genes: Past and Present, pp. 284–293, Humana Press, Clifton, N. J., 1983a
Friedman, A., Zerubavel, R., Gitler, C., and Cohen, I. R.: Molecular events in the processing of avidin by antigen-presenting cells (APC). II. Identical processing by APC ofH-2 high- and low-responder mouse strains.Immunogenetics 18: 277–289, 1983b
Germain, R. H.: Accessory cell stimulation of T cell proliferation requires active antigen processing, la restricted antigen presentation and a separate nonspecific 2nd signal.J. Immunol. 127: 1964–1966, 1981
Green, M.:Avidin. Adv. Protein Chem. 29: 85–133, 1975
Grossman, Z. and Conen, I. R.: A theoretical analysis of the phenotypical expression of immune response genes.Ear. J. Immunol. 10: 633–640, 1980
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
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 antigen.Eur. J. Immunol. 11: 382–387, 1981
Matzinger, P.: A one-receptor view of T cell behaviour.Nature 292: 497–501, 1981
Nagy, Z. A. and Klein, J.: Macrophage or T cell, that is the question.Immunol. Today 2: 288–299, 1981
Puri, J. and Lonai, P.: Mechanism of antigen binding by T cells. H-2 (I-A-restricted binding of antigen plus la by helper cells.Eur. J. Immunol. 10: 273–281, 1980
Ranghino, G., Talmon, J., Yonath, A., and Cohen, I. R.: The conformation of antigenic determinants of insulin and H-2 gene control of the immune response of T lymphocytes.In M. Balaban, J. L. Sussman, W. Traub, and A. Yonath (eds.):Structural Aspects of Recognition and Assembly in Biological Macromolecules, pp. 263–279, Balaban ISS, Rehovot, Philadelphia, 1981
Rosenthal, A. S.: Determinant selection and macrophage function in genetic control of immune responses.Immunol. Rev. 40: 135–152, 1978
Rosenthal, A. S.: Determinant selection and macrophage function.Immunol. Today 3: 33–34, 1982
Schwartz, R. H.: A clonal deletion model for Ir gene control of the immune response.Scand. J. Immunol. 7: 3–10, 1978
Schwartz, R. A., 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. A., Yano, A., Stimpfling, J. H., and Paul, W. E.: Gene complementation in the T lymphocyte proliferative response to GLO: A demonstration that both immune response genes must be expressed in the same antigen presenting cells.J. Exp. Med. 149: 40–57, 1979
Sercarz, E. E., Yowell, R. L., Turkin, D., Miller, A., Araneo, B. A., and Adorini, L.: Different functional specificity repertoires for suppressor and helper T cells.Immunol. Rev. 39: 108–136, 1978
Shevach, E.: Is determinant selection dead?Immunol. Today 3: 31–33, 1982
Skutelsky, 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
Todd, R. F., Reinharz, E. L., and Schlossman, S. F.: Human macrophagelymphocyte interaction in proliferation to soluble antigen. I. Specific deletion of lymphocyte proliferative activity on macrophage monolayers.Cell Immunol. 55: 114–121, 1980
Unanue, E. R.: The regulatory role of macrophages to antigen stimulation, Part 2. Symbiotic relationship between lymphocytes and macrophages.Adv. Immunol. 31: 1–135, 1981
Yano, A., Schwartz, R. H., and Paul, W. E.: Antigen presentation in the murine T lymphocyte proliferative response. I. Requirement for genetic identity of the major histocompatibility complex.J. Exp. Med. 146: 828–843, 1977
Ziegler, H. K. and Unanue, E. R.: Identification of a macrophage antigen processing event required for I region restricted antigen presentation to T lymphocytes.J. Immunol. 127: 1869–1875, 1981
Ziegler, H. K. and Unanue, E. R.: Decrease in macrophage antigen catabolism caused by ammonia and chloroquinine is associated with inhibition of antigen presentation to T cells.Proc. Natl. Acad. Sci. U.S.A. 79: 175–170, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Friedman, A., Zerubavel, R., Gitler, C. et al. Molecular events in the processing of avidin by antigen-presenting cells (APC). Immunogenetics 18, 291–302 (1983). https://doi.org/10.1007/BF00952967
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00952967