Immunology pp 141-155 | Cite as

The Role of Macrophages in the Processing and Presentation of Protein Antigens to T Lymphocytes

  • Thomas R. Malek
  • Ethan M. Shevach


It is clear that macrophages serve as antigen-presenting cells for a variety of specific immune responses and that many antigens are presented by macrophages to T lymphocytes in the context of the products of the I region of the major histocompatibility gene complex (MHC) of a species. For example, I-region-controlled genetic restrictions have been described for the development and expression of helper T cells (Erb and Feldmann, 1975a; Marrack and Kappler, 1978), for T-lymphocyte proliferation (Rosenthal and Shevach, 1976 Schwartz et al., 1978), and for delayed-type hypersensitivity (Miller, 1978). The use of recombinant and congenic mice and inbred guinea pigs has been an invaluable tool in establishing the role of the I region in antigen presentation. Furthermore, alloantisera to I-region gene products have demonstrated the necessity for the expression of Ia antigens on the surface of macrophages (Yamashita and Shevach, 1977; Cowing et al., 1978). The ability of multispecific anti-Ia sera to produce marked inhibition of in vitro antigen-specific T-lymphocyte proliferation to conventional and immune response (Ir) gene-controlled antigens (Shevach, 1978) indicated that a complex of Ia antigens and the nominal antigen was seen by the T lymphocyte.


Protein Antigen Major Histocompatibility Gene Complex Nominal Antigen Detergent Extraction Pulse Exposure 
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  1. Arrotti, J. J., and Garvin, J. E., 1972, Reaction of human serum albumin and human erythrocytes with tritiated 2, 4, 6-trinitrobenzene sulfonic acid and tritiated picryl chloride, Biochim. Biophys. Acta 225:79.Google Scholar
  2. Benacerraf, B., 1978, 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.PubMedGoogle Scholar
  3. Ben-Sasson, S. Z., Lipscomb, M. F., Tucker, T. F., and Uhr, J. W., 1977, The specific binding of T lymphocytes to macrophages. II. Role of macrophage-associated antigen, J. Immunol. 119:1493.PubMedGoogle Scholar
  4. Bonsall, R. W., and Hunt, S., 1971, The reactivity of the human erythrocyte membrane to sodium trinitrobenzenesulphonate, Biochim. Biophys. Acta 249:281.PubMedCrossRefGoogle Scholar
  5. Burger, R., and Shevach, E. M., 1980, Monoclonal antibodies to guinea pig Ia antigens. II. Effect on alloantigen, antigen, and mitogen induced T lymphocyte proliferation in vitro, J. Exp. Med. 152:1011.PubMedCrossRefGoogle Scholar
  6. Chesnut, R. W., Endres, R. O., and Grey, H. M., 1980, Antigen recognition by T cells and B cells: Recognition of cross-reactivity between native and denatured forms of globular antigens, Clin. Immunol. Immunopathol. 15:397.PubMedCrossRefGoogle Scholar
  7. Clark, R. B., and Shevach, E. M., 1982, 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.PubMedCrossRefGoogle Scholar
  8. Clark, R. B., Chiba, J., Zweig, S. E., and Shevach, E. M., 1982, T cell colonies recognize antigen in association with specific epitopes on Ia molecules, Nature (London) 294:412.CrossRefGoogle Scholar
  9. Cohen, D. A., and Kaplan, A. M., 1981, Adherent Ia + murine tumor lines with characteristics of dendritic cells. I. Morphology, surface phenotype, and induction of syngeneic mixed lymphocyte reaction, J. Exp. Med. 154:1881.PubMedCrossRefGoogle Scholar
  10. Comoglio, P. M., Tarone, G., and Bertini, M., 1978, Immunochemical purification of probe-Iabeled plasma membrane proteins: An approach to the molecular anatomy of the cell surface, J. Supramol. Struct. 8:301.CrossRefGoogle Scholar
  11. Cowing, C., Pincus, S. H., Sachs, D. H., and Dickler, H. B., 1978, 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.PubMedGoogle Scholar
  12. Ellner, J. J., and Rosenthal, A. S., 1975, Quantitative and immunologic aspects of the handling of 2, 4-dinitrophenyl guinea pig albumin by macrophages, J. Immunol. 114:1563.PubMedGoogle Scholar
  13. Endres, R. O., and Grey, H. M., 1980a, Antigen recognition by T cells. I. Suppressor T cells fail to recognize cross-reactivity between native and denatured ovalbumin, J. Immunol. 125:1515.PubMedGoogle Scholar
  14. Endres, R. O., and Grey, H. M., 1980b, Antigen recognition by T cells. II. Intravenous administration of native or denatured ovalbumin results in tolerance to both forms of the antigen, J. Immunol. 125:1521.PubMedGoogle Scholar
  15. Erb, P., and Feldmann, M., 1975a, The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens, J. Exp. Med. 142:460.PubMedCrossRefGoogle Scholar
  16. Erb, P., and Feldmann, M., 1975b, The role of macrophages in the generation of T helper cells. III. Influence of macrophage-derived factor in helper cell induction, Eur. J. Immunol. 5:759.PubMedCrossRefGoogle Scholar
  17. Erb, P., Feldmann, M., and Hogg, N., 1976, Role of macrophages in the generation of T helper cells. IV. Nature of genetically related factor derived from macrophages incubated with soluble antigen, Eur. J. Immunol. 6:365.PubMedCrossRefGoogle Scholar
  18. Gell, P. G. H., and Benacerraf, B., 1959, Studies on hypersensitivity. II. Delayed hypersensitivity to denatured proteins in guinea pigs, Immunology 2:64.PubMedGoogle Scholar
  19. Glimcher, L. H., Kim, K.-J., Green, I., and Paul, W. E., 1982, Ia antigen-bearing B cell tumor lines can present protein antigen and alloantigen in a major histocompatibility complex-restricted fashion to antigen-reactive T cells, J. Exp. Med. 155:445.PubMedCrossRefGoogle Scholar
  20. Ishii, N., Baxevanis, C. N., Nagy, Z. A., and Klein, J., 1981, Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains, J. Exp. Med. 154:978.PubMedCrossRefGoogle Scholar
  21. Ishizaka, K., Okudaira, H., and King, T. P., 1975, Immunogenic properties of modified antigen E. II. Ability of urea-denatured antigen and α-polypeptide chain to prime T cells specific for antigen E, J. Immunol. 114:110.PubMedGoogle Scholar
  22. Kaplan, G., Unkeless, J. C., and Cohn, Z. A., 1979, Insertion and turnover of macrophage plasma membrane proteins, Proc. Natl. Acad. Sci. USA 76:3824.PubMedCrossRefGoogle Scholar
  23. Lerner, E. A., Maris, L. A., Janeway, C. A., Jones, P. P., Schwartz, R. H., and Murphy, D. B., 1980, Monoclonal antibody against an Ir gene product, J. Exp. Med. 152:1085.PubMedCrossRefGoogle Scholar
  24. Longo, D. L., Maris, L. A., and Schwartz, R. H., 1981, Insights into immune response gene function from experiments with chimeric animals, CRC Crit. Rev. Immunol. 2:83.Google Scholar
  25. McKean, D. J., Infante, A. F., Nilson, A., Kimoto, M., Fathman, C.G., Walker, E., and Warner, N., 1981, Major histocompatibility complex-restricted antigen presentation to antigen reactive T cells by B lymphocyte tumor cells, J. Exp. Med. 154:1419.PubMedCrossRefGoogle Scholar
  26. Marrack, P., and Kappler, J., 1978, The role of H-2 linked genes in helper T cell function. III. Expression of immune response genes for trinitrophenyl conjugates of poly-L(Tyr, Glu)-poly D, L-Ala-poly-L-Lys in B cells and macrophages, J. Exp. Med. 147:1596.PubMedCrossRefGoogle Scholar
  27. Miller, J. F. A. P., 1978, Restrictions imposed on T lymphocyte reactivities by the major histocompatibility complex: Implications for T cell repertoire selection, Immunol. Rev. 42:76.CrossRefGoogle Scholar
  28. Pierce, C. W., Kapp, J. A., and Benacerraf, B., 1976, Regulation by the H-2 gene complex of macrophage-lymphoid cell interactions in secondary antibody responses in vitro, J. Exp. Med. 144:371.CrossRefGoogle Scholar
  29. Puri, J., and Lonai, P., 1980, Mechanism of antigen-binding by T cells: H-2 (I-A)-restricted binding of antigen plus Ia by helper cell, Eur. J. Immunol. 10:273.PubMedCrossRefGoogle Scholar
  30. Rosenthal, A. S., 1978, Determinant selection and macrophage function in genetic control of the immune response, Immunol. Rev. 40:136.PubMedCrossRefGoogle Scholar
  31. Rosenthal, A. S., and Shevach, E. M., 1976, The function of macrophages in T-lymphocyte antigen recognition, Contemp. Top. Immunobiol. 5:47.PubMedGoogle Scholar
  32. Schirrmacher, V., and Wigzell, H., 1972, Immune responses against native and chemically modified albumins in mice. I. Analysis of non-thymus-processed (B) and thymus-processed (T) cell responses against methylated bovine serum albumin, J. Exp. Med. 136:1616.PubMedCrossRefGoogle Scholar
  33. Schwartz, R. H., Yano, A., and Paul, W. E., 1978, Interaction between antigen-presenting cells and primed T lymphocytes, Immunol. Rev. 40:153.PubMedCrossRefGoogle Scholar
  34. Shevach, E. M., 1978, The guinea pig I-region: A functional analysis of Ia-Ir associations, Springer Semin. Immunopathol. 1:207.CrossRefGoogle Scholar
  35. Shevach, E. M., 1980, The role of antigenic determinants in macrophage-T lymphocyte interaction, in: Macrophage Regulation of Immunity (E. R. Unanue and A. S. Rosenthal, eds.), p. 59, Academic Press, New York.Google Scholar
  36. Shevach, E. M., Chan, C., Thomas, D. W., and Clement, L. T., 1979, What is the nature of the antigenic complex recognized by T lymphocytes?, in: T and B Lymphocytes: Recognition and Function (F. H. Bach, B. Bonavida, E. S. Vitetta, and G. F. Fox, eds.), p. 405, Academic Press, New York.CrossRefGoogle Scholar
  37. Steinman, R. M., and Cohn, Z. A., 1973, The interaction of soluble horseradish peroxidase with mouse peritoneal macrophages in vitro, J. Cell Biol. 55:186.CrossRefGoogle Scholar
  38. Takatsu, K., and Ishizaka, K., 1975, Reagenic antibody formation in the mouse. VI. Suppression of IgE and IgG antibody responses to ovalbumin following the administration of high dose urea-denatured antigen, Cell. Immunol. 20:276.PubMedCrossRefGoogle Scholar
  39. Thomas, D. W., Clement, L. T., and Shevach, E. M., 1978, T lymphocyte stimulation by hapten-conjugated macrophages: A model system for the study of immunocompetent cell interactions, Immunol. Rev. 40:181.PubMedCrossRefGoogle Scholar
  40. Uhr, J. W., and Pappenheimer, H. M., Jr., 1958, Delayed hypersensitivity. II. Induction of hypersensitivity in guinea pigs by means of antigen-antibody complexes, J. Exp. Med. 108:891.PubMedCrossRefGoogle Scholar
  41. Unanue, E. R., 1981, The regulatory role of macrophages in antigenic stimulation. Part two. Symbiotic relationship between lymphocytes and macrophages, Adv. Immunol. 31:1.PubMedCrossRefGoogle Scholar
  42. Unanue, E. R., and Cerottini, J. C., 1970, The immunogenicity of antigen bound to the plasma membrane of macrophages, J. Exp. Med. 131:711.PubMedCrossRefGoogle Scholar
  43. Yamashita, U., and Shevach, E. M., 1977, The expression of Ia antigens on immunocompetent cells in the guinea pig. II. Ia antigens on macrophages, J. Immunol. 119:1584.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Thomas R. Malek
    • 1
  • Ethan M. Shevach
    • 1
  1. 1.Laboratory of Immunology, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA

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