Structural Considerations of T-Cell Cognizance of Antigen

  • Eli Benjamini
  • Beatrice C. Langton
  • Carl E. Mackewicz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 225)


Work summarized herein describes two congenic strains of mice, C57BL/10 and B10.BR, which differ at the I-A region of the MHC where C57BL/10 and B10.BR are I-Ab and I-Ak respectively. Using various antigens to stimulate, in vitro, primed T lymphocytes, studies on the responsiveness of these two strains to immunization with TMVP and with its tryptic peptide number 8 representing residues 93–112 of the protein are described. These studies revealed that in the C57BL/10 strain TMVP and peptide 8 exhibit cross reactivity on the T-cell level, whereas in the B10.BR strain these two antigens do not exhibit such cross reactivity. Further studies revealed that the cross reactivity is mapped to the I-A region of the MHC with cross reactivity between TMVP and peptide 8 exhibited in mice with I-Ab (referred to as cross reactive-CR) but not with I-Ak (referred to as non cross reactive-NCR). Cell depletion and reconstitution experiments revealed that cross reactivity (or the lack thereof) could be attributed to antigen presenting cells (APC). A profound difference between the strains was also expressed on the level at which their immune T-cells reacted in vitro to stimulation by various derivatives of peptide 8. The studies suggest that the strains differ in their responsiveness to the various orientations in which the T-cell epitope(s) are presented. Assuming that TMVP, but not peptide 8, is altered during processing by APC and assuming that antigen processing by APC of CR and NCR is similar, the difference which the strains exhibit in recognizing different orientations of the epitope may account for the difference in the cross reactivity between TMVP and peptide 8 exhibited by these strains. Further investigations revealed that the strains also differ in their response to pre-immunization with TMVP prior to immunization with peptide 8. Whereas preimmunization of the C57BL/10 (CR) mice with TMVP did not affect subsequent response to immunization with peptide 8, preimmunization of B10.BR (NCR) mice with TMVP suppressed the response to subsequent immunization with peptide 8. It is suggested that the presentation of the T-cell epitope(s) in the correct orientation by the appropriate Ia is crucial for the activation of T helper cells but that such presentation does not play a decisive role in the activation of T suppressor cells.


Antigen Present Cell Cross Reactive Helper Cell Peritoneal Exudate Cell Reconstitution Experiment 
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  1. 1.
    Anderer, F.A., Uhlig, H., Weber, E., and Schramm, G., 1960, Nature, 186: 922.PubMedCrossRefGoogle Scholar
  2. 2.
    Babbit, B.P., Allen, P.H., Matsueda, G. E., and Unanue, E.R., 1985, Nature (London) 317: 359.Google Scholar
  3. 3.
    Benjamini, E., 1977, in: Immunochemistry of Proteins, Vol. 2, M.Z. Atassi, ed., Plenum Press, New York.Google Scholar
  4. 4.
    Benjamini, E., Wan, A.M., Langton, B.C., and Andria, M.L., 1985, in: High Technology Route to Virus Vaccines, G.R. Dreesman, J.G. Bronson, and R. Kennedy, eds., Am. Soc. Microbiol., Pub., Washington, D.C.Google Scholar
  5. 5.
    Benjamini, E., Langton, B.C., Wan, A.M., Andria, M.L., and Leung, C.Y. 1986, in: Immunomodulation, G. Torrigiani, ed., W.H.O. Pub., Geneva (in press).Google Scholar
  6. 6.
    Benjamini, E., Langton, B.C., and Wan, A.M., 1986, Fed. Proc., 45: 726.Google Scholar
  7. 7.
    Champness, J.N., Bloomer, A.C., Bricogne, G., Butler, P.J.G., and Klug, A., 1976, Nature, 259: 20.PubMedCrossRefGoogle Scholar
  8. 8.
    Dorf, E.M., and Benecerraf, B., 1985, Immunol. Rev., 83: 23.PubMedCrossRefGoogle Scholar
  9. 9.
    Friedman, A., Zerubavel, R., Gitler, C., and Cohen, I.R., 1983, Immunogenetics, 18: 277.PubMedCrossRefGoogle Scholar
  10. 10.
    Geha, R.S., Milgrom, H., Broff, M., Alpert, S., and Yunis, E.J., 1979, Proc. Natl. Acad. Sci. (U.S.), 76: 4038.CrossRefGoogle Scholar
  11. 11.
    Heber-Katz, E., Hansburg, D., and Schwartz, R.H., 1983, J. Mol. Cell. Immunol., 1: 3.PubMedGoogle Scholar
  12. 12.
    Kappler, J.W., and Marrack, P., 1978, J. Exp. Med., 148: 1510.PubMedCrossRefGoogle Scholar
  13. 13.
    Morrow, P.R., Rennick, D.M., and Benjamini, E., 1983, J. Immunol., 131: 2875.PubMedGoogle Scholar
  14. 14.
    Paul, W.E., Shevach, E.M., Pickeral, S., Thomas, D.W., and Rosenthal, A.S., 1977, J. Exp. Med., 145: 618.PubMedCrossRefGoogle Scholar
  15. 15.
    Paul, W.E., 1984, in: Fundamental Immunology, W.E. Paul, ed., Raven Press, New York.Google Scholar
  16. 16.
    Rosenthal, A.S., and Shevach, E.M., 1973, J. Exp. Med., 138: 1194.PubMedCrossRefGoogle Scholar
  17. 17.
    Schrier, R.D., Skidmore, B.J., Kurnick, J.T., Goldstine, S.N., and Chiller, J.M., 1979, J. Immunol., 123: 2525.PubMedGoogle Scholar
  18. 18.
    Schwartz, R.H., 1985, Ann. Rev. Immunol., 3: 237.CrossRefGoogle Scholar
  19. 19.
    Shastri, N., Gammon, G., Miller, A., and Sercarz, E.E., 1986. J. Exp. Med., 164: 882.PubMedCrossRefGoogle Scholar
  20. 20.
    Shevach, E.M., and Rosenthal, A.S., 1973, J. Exp. Med., 138: 1213.PubMedCrossRefGoogle Scholar
  21. 21.
    Shimonkevitz, R., Colon, S., Kappler, J.W., Marrack, P., and Grey, H.M., 1984, J. Immunol., 133: 2067.PubMedGoogle Scholar
  22. 22.
    Thomas, D.W., and Shevach, E.M., 1977, Proc. Natl. Acad. Soi. (U.S.A.), 74: 2104.CrossRefGoogle Scholar
  23. 23.
    Tsugita, A.D., Gish, D., Young, J.D., Fraenkel-Conrat, H., Knight, C.A., and Stanley, W.M., 1960, Proc. Natl. Acad. Sci. (U.S.A.), 46: 1463.CrossRefGoogle Scholar
  24. 24.
    Unanue, E.R., 1984. Ann. Rev. Immunol., 2: 395.CrossRefGoogle Scholar
  25. 25.
    Wan, A.M., Langton, B.C., Andria, L., and Benjamini, E., 1986, Mol. Immunol., 23: 467.PubMedCrossRefGoogle Scholar
  26. 26.
    Woody, B.R., and Knight, C.A., 1959, Virology, 9: 359.PubMedCrossRefGoogle Scholar
  27. 27.
    Yano, A., Schwart, R.H., and Paul, W.E., 1978, Eur. J. Immunol., 8: 344.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Eli Benjamini
    • 1
  • Beatrice C. Langton
    • 1
  • Carl E. Mackewicz
    • 1
  1. 1.Department of Medical Microbiology and Immunology School of MedicineUniversity of Calif. DavisUSA

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