Abstract
A series of known sequential polypeptides is being synthesized and used in our laboratory to study the contribution of antigen structure, i. e., amino acid sequence and conformation in antigen recognition and specificity of the immune response. The capacity to respond to one such α-helical polypeptide (T-G-A-Gly)n, is T-cell dependent and restricted to mice of theH- 2b haplotype. The response is controlled by anIr gene mapping to theK region and/or theIA subregion which allows the animal to make both a T-cell mediated response, as well as a humoral response to the polypeptide. The response of three mutant strains at theK end of the major histocompatibility locus (MHC) need not differ from that of the responder parental haplotype.
PETLES obtained from mice possessing a responder haplotype proliferate when cultured in vitro with (T-G-A-Gly)n. The antibody level of individual inbred mice of a given strain at a given time differs significantly (from 80% binding to less than 10% antigen bound in 3 out of 57 mice). There is also great individual variability in time of appearance of the antibody response and where peak optimal levels are seen. Possible explanations for the variation in the antibody expression include: (a) the polymer is a weak immunogen, (b) the presence of modifier gene(s) outside of the major histocompatibility complex controlling the magnitude of the antibody level, (c) the possible effect of the polymer which is a B cell mitogen as a generator of suppressor T cells and, (d) a feedback mechanism effect on B cells controlling the antibody level.
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Berzofsky, J. A., Schechter, A. N., Shearer, G. M., and Sachs, D. H.: Genetic control of the immune response to staphylococcal nuclease. III. Time course and correlation between the response to native nuclease and the response to its polypeptide fragments.J. Exp. Med. 145:111–122, 1977
Calkins, C. E., Orbach-Arbouys, S., Stutman, S., and Gershon, R. K.: Cell interactions in the suppression ofin vitro antibody response.J. Exp. Med. 143:1421–1428, 1976
Dorf, M. E., Dunham, E. K., Johnson, J. P., and Benacerraf, B.: Genetic control of the immune response: the effect of non-H-2 linked genes on antibody production.J. Immunol. 112:1329–1336, 1974
Hunter, W. M.: Radioimmunoassay.In D. M. Weir (ed.):Handbook of Experimental Immunology, pp. 17.1–17.35, F. A. David and Co., Philadelphia, 1973
Lai, C. H. and Maurer, P. H.: Immune responses of inbred guinea pigs to the sequential polymer poly(L-Tyr-Glu-Ala-Gly): studies with the oligomers of the polymers.J. Immunol. 119:842–846, 1977
Markham, R.: A steam distillation apparatus suitable for micro-Kjeldahl analysis.Biochem. J. 36:790–791, 1942
Maurer, P. H. and Merryman, C. F.: Genetic control of immune responses of inbred mice: responses against terpolymerspoly (Glu57Lys38Ala5) and poly(Glu54Lys36Ala10).Immunogenetics 1:174–183, 1974
Maurer, P. H., Odstrchel, G., and Merryman, C. F.: Genetic control of the immune response in guinea pigs to the known sequence polymer (Tyr-Glu-Ala-Gly)n.J. Immunol. 111:1018–1021, 1973
Maurer, P. H., Merryman, C. F., and Jones, J.: Multigenic control of immune responses of inbred mice against the terpolymers poly (Glu57Lys38Ala5) and poly(Glu54Lys36Ala10) and linkage with H-2 haplotype.Immunogenetics 1:398–406, 1974
Maurer, P. H., Merryman, C. F., Zeiger, A. R., Lai, C. H., and Jolly, J.: In vivo (genetic) and in vitro immune responses of mice to the known sequence polymer poly(Tyr-Glu-Ala-Gly).Fed. Proc. 34:978, 1975 (Abstract)
Melchers, F. H., von Boehmer, H., and Phillips, R. A.: Blymphocyte subpopulations in the mouse. Organ distribution and ontogeny of immunoglobulin-synthesizing and mitogen-sensitive cells.Transplant. Rev. 25:26–58, 1975
Merryman, C. F. and Maurer, P. H.: Genetic control of immune response to glutamic acid, alanine, tyrosine containing copolymers in mice.J. Immunol. 108:135–141, 1972
Merryman, C. F. and Maurer, P. H.: Genetic control of immune response against random copolymers of glutamic acid and alanine (GA) and tyrosine (GT) in inbred mice.J. Immunol. 116:739–742, 1976
Merryman, C. M., Maurer, P. H., and Zeiger, A. R.: Genetic control of two independently segregating loci in mice to the sequential polypeptide (Tyr-Glu-Ala-Gly)n.Immunogenetics 4:373–380, 1977
Rosenstreich, D. L., Blake, J. T., and Rosenthal, A. S.: The peritoneal exudate lymphocyte. 1. Differences in antigen responsiveness between peritoneal exudate and lymph node lymphocytes from immunized guinea pigs.J. Exp. Med. 134:1170–1186, 1971
Schwartz, R. H., Jackson, L., and Paul, W. E.: T-lymphocyte enriched peritoneal exudate cells. I. Reliable assay for antigen induced T-lymphocyte proliferation.J. Immunol. 115:1330–1338, 1975
Zeiger, A. R. and Maurer, P. H.: Genetic control of immune response in guinea pigs to the known sequence polymer (Tyr-Ala-Glu-Gly)n.J. Immunol. 117:708–710, 1976
Zeiger, A. R., Lai, C.-H., and Maurer, P. H.: Synthesis of poly (L-Tyr-L-Glu-L-Ala-Gly) and poly (L-Lys-L-Glu-L-Ala) and their circular dichroism spectra in aqueous solution.Biopolymers 14:2281–2295, 1975
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This work was supported in part by the following grants: The National Institute of Allergy and Infectious Diseases A107825; American Cancer Society Grant IM-5F; National Foundation-March of Dimes 1-492.
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Merryman, C.F., Maurer, P.H., Lai, CH. et al. Murine responses to (Tyr-Glu-Ala-Gly)n . Immunogenetics 9, 183–192 (1979). https://doi.org/10.1007/BF01570409
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DOI: https://doi.org/10.1007/BF01570409