The Genetics of the Immune Response to Trichinella spiralis Antigens in the Mouse

  • Michael Robinson
  • Chella S. David


The production and successful utilization of a defined vaccine against a parasitic infection requires an understanding of the complex processes which occur during the development of most parasites, including the stage of the life cycle which can be effectively combatted by the host’s immune system. For the activation of the host’s immune system against any antigen there are many genetically controlled physical parameters involved, of which probably the most crucial are the interactions of the T cell receptor and the antigen/Major Histocompatibility Complex (MHC) molecules. In the case of many parasites, these particular molecular interactions have only recently been investigated. Although for several years it had been appreciated that there is a significant genetic element controlling the host’s immune response to parasites, the actual nature of these controlling elements had not been elucidated (Wassom, 1985; Behnke and Robinson, 1985; Wakelin, 1985). However, recent appraisals of trends and patterns in the genetic make-up of hosts which can be categorized as good or bad responders to particular parasites has led us to realize that the known genotype of animals which respond to parasitic infections are not just epiphenomena but actually are an indication of controlling molecular properties. This is particularly true of the immune response to Trichinella spiralis in the mouse, the host/parasite system which has revealed the most data concerning the significance of the host genotype (Wassom et al., 1984).


Major Histocompatibility Complex Adult Worm Host Genotype Muscle Larva Newborn Larva 
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  1. Abe, R. and Hodes, R.J. (1988) T cell recognition of Mlsc. I. Influence of MHC gene products in Mlsc-specific T cell recognition. J. Immunol. 140:4132–4138.PubMedGoogle Scholar
  2. Almond, N.M. and Parkhouse, R.M.E. (1985) Nematode Antigens. IN: Current Topics in Microbiology and Immunology 120: Parasite Antigens in Protection, Diagnosis and Escape. Springer-Verlag, Berlin,Heidelberg, pp. 173.Google Scholar
  3. Baxavenis, C.N., Ishii, N., Nagy, Z.A., Klein, J. (1982) Role of the Ek molecule in the generation of suppressor T cells in response to LDHβ. Scand. J. Immunol. 16:25.CrossRefGoogle Scholar
  4. Behnke, J.M. and Robinson, M. (1985) Genetic control of immunity to Nematospiroides dubius: a nine-day anthelmintic abbreviated immunizing regime which separates weak and strong responder strains of mice. Parasite Immunol. 7:235.PubMedCrossRefGoogle Scholar
  5. Bell, R.G., McGregor, D.D., and Adams, L.S. (1982) Trichinella spiralis: genetic basis for differential expression of phase-specific intestinal immunity in mice. Exp. Parasitol. 53:315.PubMedCrossRefGoogle Scholar
  6. Bell, T.G., McGregor, D.D., and Despommier, D.D. (1979) Trichinella spiralis: mediation of the intestinal component of protective immunity in the rat by multiple phase-specific anti-parasite responses. Exp. Parasitol. 47:140.PubMedCrossRefGoogle Scholar
  7. Blackman, M., Yague, J., Kubo, R., Grey, D., Coleclough, C., Palmer, E. Kappler, J., and Marrack, P. (1986) The T cell repertoire may be biased in favor of MHC recognition. Cell 47:349.PubMedCrossRefGoogle Scholar
  8. Blackwell, J.M. and Roberts, M.B. (1987) Immunomodulation of murine visceral leichmaniasis by administration of monoclonal anti-Ia antibodies: differential effects of anti-I-A vs. anti-I-E antibodies. Eur. J. Immunol. 17:1669.PubMedCrossRefGoogle Scholar
  9. Buus, S., Sette, A., Colon, S.M., Miles, C. and Grey, H.M. (1987) The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science 235:1353.PubMedCrossRefGoogle Scholar
  10. Chipman, P.B. (1957) The antigenic role of excretions and secretions of adult Trichinella spiralis in the production of immunity in mice. J. Parasitol. 43:593.PubMedCrossRefGoogle Scholar
  11. Coffman, R., Ohara, J., Bond, M., Carty, J., Zlotnik, A. and Paul, W.E. (1986) B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide activated B cells. J. Immunol. 136:4358.Google Scholar
  12. Coffman, R.L., Seymour, B.W.P., Lebman, D.A., Hiraki, D.D., Christiansen, J.A., Shrader, B., Cherwinski, H.M., Savelkoul, H.F.J., Finkelman, F.D., Bond, M.W. and Mosmann, T.R. (1988) The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol. Rev. 102:5.PubMedCrossRefGoogle Scholar
  13. Crandall, R.B. and Crandall, C.A. (1972) Trichinella spiralis: immunologic response to infection in mice. Exp. Parasitol. 31:378.PubMedCrossRefGoogle Scholar
  14. David, C.S. (1976) Serologic and genetic aspects of murine la antigens. Transplant. Rev. 30:299.PubMedGoogle Scholar
  15. Despommier, D.D. and Laccetti, A. (1981) Trichinella spiralis: partial characterization of antigens isolated by immuno-affinity chromatography from the large particle fraction of the muscle larvae. J. Parasitol. 67(3):332.PubMedCrossRefGoogle Scholar
  16. Gamble, H.R. (1985) Trichinella spiralis: immunization of mice using monoclonal antibody affinity-isolated antigens. Exp. Parasitol. 59:398–404.PubMedCrossRefGoogle Scholar
  17. Golinska, Z., and Bany, J. (1976) Serum immunoglobulins in inbred mice strains infected with Trichinella spiralis and Trichinella pseudospiralis. In: Trichinellosis, Kim, C., and Pawlowski, A., eds. University of New England Press, Hanover, NH, p. 151.Google Scholar
  18. James, E.R., and Denham, D.A. (1974) The stage specificity of the immune response to Trichinella spiralis. In: Trichinellosis, Kim, C., eds. Intent Publishing, New York, p. 345.Google Scholar
  19. Jones, P.P., Murphy, D. B. and McDevitt, H.O. (1981) Variable synthesis and expression of Eα and Ae (Eß) Ia polypeptide chains in mice of different H-2 haplotypes. Immunogenetics 12:321.PubMedCrossRefGoogle Scholar
  20. Kappler, J.W., Roehm, N. and Marrack, P. (1987) T cell tolerance by clonal elimination in the thymus. Cell 49:273.PubMedCrossRefGoogle Scholar
  21. Kappler, J.W., Staertz, Y., White, J. and Marrack, P.C. (1988) Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature 332:35.PubMedCrossRefGoogle Scholar
  22. Kappler, J.W., Wade, I., White, J., Kushnir, E., Blackman, M., Bill, M., Roehm, N., and Marrack, P. (1987) A T cell receptor Vß segment that imparts reactivity to a class II major histocompatibility complex product. Cell 49:263.PubMedCrossRefGoogle Scholar
  23. Kazura, J.W. and Grove, D.I. (1978) Stage-specific antibody-dependent eosinophil-mediated destruction of Trichinella spiralis. Nature 274:588.PubMedCrossRefGoogle Scholar
  24. Krco, C.J., Wassom, D.L., Abramson, E.J. and David, C.S. (1983) Cloned T cells recognize Trichinella spiralis antigen in association with an Ek restriction element. Immunogen. 18:435–444.CrossRefGoogle Scholar
  25. Larsh, J.E. Jr. (1963) Experimental trichinosis. Adv. Parasitol 1:213.PubMedCrossRefGoogle Scholar
  26. Larsh, J.E. and Weatherly, N.F. (1975) Cell mediated immunity against certain parasitic worms. Adv. Parasitol. 13:183.PubMedCrossRefGoogle Scholar
  27. MacDonald, H.R., Schneider, R., Lees, R.K., How, R.C., Acha-Orbea, H., Festenstein, H., Zinkernagel, R.M., and Hengartner, H. (1988) T cell receptor Vß use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature 332:40.PubMedCrossRefGoogle Scholar
  28. Maizels, R.M., Kennedy, M.W., Meghji, M., Robertson, B.D. and Smith, H.V. (1987) Shared carbohydrate epitopes on distinct surface and secreted antigens of the parasitic nematode Tonorara canis. Journal of Immunology 139:207–214.Google Scholar
  29. Maloney, A. and Denham, D.A. (1979) Effects of immune serum and cells on newborn larvae of Trichinella spiralis. Parasite Immunol. 1:3.CrossRefGoogle Scholar
  30. Marti, H.P., Murrell, K.D. and Gamble, H.R. (1987) Trichinella spiralis: immunization of pigs with newborn larval antigens. Exp. Parasitol. 63:68.PubMedCrossRefGoogle Scholar
  31. Mathis, D.J., Benoist, C., Williams, V.E., Kanter, M., and McDevitt, H.O. (1983) Several mechanisms can account for defective Eα gene expression in different mouse haplotypes. Proc. Natl. ACad. Sci. USA 80:273.PubMedCrossRefGoogle Scholar
  32. Matis, L.A., Sorger, S.B., McElligot, D.L., Fink, P.J. and Hedrick, S.M. (1987) The molecular basis of alloreactivity in antigen-specific, major histocompatibility complex-restricted T cell clones. Cell 51:59.PubMedCrossRefGoogle Scholar
  33. Miller, H.R.P. (1984) The protective mucosal response against gastrointestinal nematodes in ruminants and laboratory animals. Vet. Immunol. and Immunopathol. 6:167.CrossRefGoogle Scholar
  34. Morel, P.A., Livingstone, A.M., and Fathman, C.G. (1987) Correlation of T cell receptor Vß gene family with MHC restriction. J. Exp. Med. 166:583.PubMedCrossRefGoogle Scholar
  35. Mossmann, T.R., Sherwinski, H., Bond, M.W., Giedlin, M.A. and Coffman, R.L. (1986) Two types of murine helper T cell clones. 1) Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136:2348.Google Scholar
  36. Murphy, D.B., Jones, P.P., Loken, M.R. and McDevitt, H.O. (1980) Interaction between I region loci influences the expression of a cell surface la antigen. Proc. Natl. Acad. Sci. USA 77:5405.Google Scholar
  37. Oliveira, D.B.G., Blackwell, N., Virchis, A.E. and Axelrod, R.A. (1985) T helper and T suppressor cells are restricted by the A and E molecules, respectively, in the F antigen system. Immunogenetics 22:169.PubMedCrossRefGoogle Scholar
  38. Ortega-Pierres, G., Mackenzie, C.D. and Parkhouse, R.M.E. (1984) Protection against Trichinella spiralis induced by a monoclonal antibody that promotes killing of newborn larvae by granulocytes. Parasite Immunol. 6:275.PubMedCrossRefGoogle Scholar
  39. Powers, G.D., Abbas, A.K., and Miller, R. A. (1988) Frequencies of IL-2 and IL-3 secretory T cells in naive and antigen-stimulated lymophocyte populations. J. Immunol. 140:3352.PubMedGoogle Scholar
  40. Puri, J., Lonai, P. and Friedman, V. (1986) Antigen-Ia interaction and the proteolytic processing of antigen: the structure of the antigen determines its restriction to the A or E molecule of the major histocompatibility complex. Eur. J. Immunol. 16:1093.PubMedCrossRefGoogle Scholar
  41. Quintans, J., Suzuki, H., Sosman, J.A. and Shah, P.D. (1986) Immunoregulation by T cells. 1) Characterization of the I-Ek-specific Lbd self-reactive T cell clone that helps, suppresses and contrasuppresses B cell responses. J. Immunol. 136:1974.PubMedGoogle Scholar
  42. Rivera-Ortiz, G.I. and Nussenzweig, R. (1976) Trichinella spiralis: anaphylactic antibody formation and susceptibility in strains of inbred mice. Exp. Parasitol. 39:7.PubMedCrossRefGoogle Scholar
  43. Robinson, M., Benhke, J.M. and Williams, D.J.L. (1988) Immunity to Heligmosomoides polygyrus (Nematospiroides dubius): survival or rejection of adult worms following transplantation to mice refractory to larval challenge. J. Helminthol. (in press).Google Scholar
  44. Ruddle, N.H. (1987) Tumor necrosis factor and related cytotoxins. Immunology Today 8:129.CrossRefGoogle Scholar
  45. Sette, A., Buus, S., Colon, S., Miles, C., and Grey, H. (1988) I-Ad binding peptides derived from unrelated protein antigens share a common structural motif. J. Immunol. 141:45.PubMedGoogle Scholar
  46. Silberstein, D.S. and Despommier, D.D. (1984) Antigens from Trichinella spiralis that induce a protective response in the mouse. J. Immunol. 132:898.PubMedGoogle Scholar
  47. Silberstein, D.S. and Despommier, D.D. (1985) Effects on Trichinella spiralis of host responses to purified antigens. Science 227:948.PubMedCrossRefGoogle Scholar
  48. Smithers, S.R. and Terry, R. J. (1969) Immunity in schistosomiasis. Ann. N.Y. Acad. Sci. 160:826.PubMedCrossRefGoogle Scholar
  49. Ubeira, F.M., Leiro, J., Santamarina, M.T., Villa, T.G. and SanMartin-Ovran, M.L. (1987) Immune response to Trichinella epitopes: the antiphosphorylcholine plaque-forming cell response during the biological cycle. Parasitology 94:543–553.PubMedCrossRefGoogle Scholar
  50. Vitetta, E.S., Ohara, J., Myers, C., Layton, J., Krammer, P.H. and Paul, W.E. (1985) Serological, biochemical and functional identity of B cell-stimulatory factor-1 and B cell differentiation factor for IgGl. J. Exp. Med. 162:1726.PubMedCrossRefGoogle Scholar
  51. Wakelin, D. (1985) Genetic control of immunity to helminth infections. Parasitology Today 1:17.PubMedCrossRefGoogle Scholar
  52. Wakelin, D., Donachie, A.M. (1981) Genetic control of immunity to Trichinella spiralis. Donor bone marrow cells determine responses to infection in mouse radiation chimaeras. Immunology 43:787.PubMedGoogle Scholar
  53. Wakelin, D. and Donachie, A.M. (1983) Genetic control of immunity to Trichinella spiralis. Influence of H-2 linked genes on immunity to the intestinal phase of infection. Immunology 48:343.PubMedGoogle Scholar
  54. Wassom, D.L. (1985) Genetic control of the host response to parasite helminth infections. In: Genetic Control of Host Resistance to Infection and Malignancy (Skamene, E., ed.) Alan R. Liss, New York, p. 449.Google Scholar
  55. Wassom, D.L., Brooks, B.O., Babish, J.G., and David, C. S. (1983) A gene mapping between the S and D regions of the H-2 complex influences resistance to Trichinella spiralis infections in mice. J. Immunogen. 10:371.CrossRefGoogle Scholar
  56. Wassom, D.L., Brooks, B.O. and Cypess, R.H. (1983) Trichinella spiralis: Role of non-H-2 genes in resistance to primary infection. Exp. Parasitol. 55:153.PubMedCrossRefGoogle Scholar
  57. Wassom, D.L., David, C.S. and Gleich, G.J. (1979) Genes within the major histocompatibility complex influence susceptibility to Trichinella spiralis in the mouse. Immunogen. 9:491.CrossRefGoogle Scholar
  58. Wassom, D.L., David, C.S. and Gleich, G.J. (1980) MHC linked genetic control of the immune response to parasites: Trichinella spiralis in the mouse. In: Genetic Control of Natural Resistance to Infection and Malignancy (Eds. E. Skamene, P.A.L. Kongshown and M. Landy) Academic Press, Inc., New York, p. 75.CrossRefGoogle Scholar
  59. Wassom, D.L., Dougherty, D.A., Krco, C.J. and David, C.S. (1984) H-2 controlled, dose dependent suppression of the response that expels adult Trichinella spiralis from the small intestine of mice. Immunology 53:811.PubMedGoogle Scholar
  60. Wassom, D.L., Krco, C.J., and David, C.S. (1987) I-E suppression and susceptibility to parasite infections. Immunology Today 2:39.CrossRefGoogle Scholar
  61. Wassom, D.L., Wakelin, D., Brooks, B.O., Krco, C.J. and David, C.S. (1984) Genetic control of immunity to Trichinella spiralis infections of mice. Hypothesis to explain the role of H-2 genes in primary and challenge infections. Immunology 51:625.PubMedGoogle Scholar
  62. Williams, D.J.L. and Behnke, J.M. (1983) Host protective antibodies and serum immunoglobulin isotypes in mice chronically infected or repeatedly immunized with the nematode parasite Nematospiroides dubius. Immunology 348:34.Google Scholar
  63. Winoto, A., Urgan, J.L., Lan, N.C., Goverman, J., Hood, L., and Hansburg, D. (1986) Predominant use of a Va gene segment in mouse T-cell receptors for cytochrome C. Nature 324:679.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Michael Robinson
    • 1
  • Chella S. David
    • 1
  1. 1.Department of ImmunologyMayo ClinicRochesterUSA

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