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. 1986 Jul 1;164(1):196–210. doi: 10.1084/jem.164.1.196

Immunization with SV40-transformed cells yields mainly MHC-restricted monoclonal antibodies

PMCID: PMC2188216  PMID: 3014034

Abstract

Recognition of antigens on cell surfaces only in the context of the MHC- encoded alloantigens of the presenting cell (self + X) has classically been considered the province of T cells. However, evidence from several sources has indicated that B cells and antibodies can exhibit self + X- restricted recognition as well. This report concerns the mAb response to SV40-transformed H-2b fibroblast cell lines. The specificities of the antibodies obtained have been analyzed for binding to a panel of SV40-transformed H-2-syngeneic, H-2-allogeneic, and H-2b mutant fibroblast cell lines, as well as cell lines not bearing cell surface SV40 transformation-associated antigens. A large proportion of primary C57BL/6 (71%) and BALB/c (68%) splenic B cells responding to in vitro stimulation with SV40-transformed H-2b cells recognize cell surface antigens associated with SV40 transformation only when coexpressed with MHC antigens of the immunizing cell, particularly the Kb molecule, on transformed cells. To extensively define the nature of antigen recognition by these antibodies, we have generated and characterized nine hybridoma antibodies specific for SV40-transformed H-2-syngeneic cell lines. Seven of these hybridoma antibodies recognize SV40- associated transformation antigens in the context of H-2b molecules. Six of these are restricted by the Kb molecule and discriminate among a panel of SV40-transformed Kb mutant cell lines, thus confirming the participation of class I MHC-encoded molecules in the recognition by B cells of cell surface antigens.

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Selected References

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  1. Amit A. G., Mariuzza R. A., Phillips S. E., Poljak R. J. Three-dimensional structure of an antigen-antibody complex at 6 A resolution. Nature. 1985 Jan 10;313(5998):156–158. doi: 10.1038/313156a0. [DOI] [PubMed] [Google Scholar]
  2. Amzel L. M., Poljak R. J., Saul F., Varga J. M., Richards F. F. The three dimensional structure of a combining region-ligand complex of immunoglobulin NEW at 3.5-A resolution. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1427–1430. doi: 10.1073/pnas.71.4.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  4. 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. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  5. Bevan M. J. Interaction antigens detected by cytotoxic T cells with the major histocompatibility complex as modifier. Nature. 1975 Jul 31;256(5516):419–421. doi: 10.1038/256419a0. [DOI] [PubMed] [Google Scholar]
  6. Carroll R. B., Goldfine S. M., Melero J. A. Antiserum to polyacrylamide gel-purified simian virus 40 T antigen. Virology. 1978 Jun 1;87(1):194–198. doi: 10.1016/0042-6822(78)90171-x. [DOI] [PubMed] [Google Scholar]
  7. Crawford L. V., Lane D. P., Denhardt D. T., Harlow E. E., Nicklin P. M., Osborn K., Pim D. C. Characterization of the complex between SV40 large T antigen and the 53K host protein in transformed mouse cells. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):179–187. doi: 10.1101/sqb.1980.044.01.021. [DOI] [PubMed] [Google Scholar]
  8. Crawford L. V., Pim D. C., Lane D. P. An immunochemical investigation of SV40 T-antigens. 2. Quantitation of antigens and antibody activities. Virology. 1980 Jan 30;100(2):314–325. doi: 10.1016/0042-6822(80)90522-x. [DOI] [PubMed] [Google Scholar]
  9. Denis K. A., Klinman N. R. Genetic and temporal control of neonatal antibody expression. J Exp Med. 1983 Apr 1;157(4):1170–1183. doi: 10.1084/jem.157.4.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Doherty P. C., Biddison W. E., Bennink J. R., Knowles B. B. Cytotoxic T-cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype. J Exp Med. 1978 Aug 1;148(2):534–543. doi: 10.1084/jem.148.2.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Galfre G., Howe S. C., Milstein C., Butcher G. W., Howard J. C. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature. 1977 Apr 7;266(5602):550–552. doi: 10.1038/266550a0. [DOI] [PubMed] [Google Scholar]
  12. Gooding L. R. Anomalous behavior of H-2Kb in immunity to syngeneic SV40 transformed cells: evidence for cytotoxic T cell recognition of H-2/SV40 membrane antigen complexes. J Immunol. 1980 Apr;124(4):1612–1619. [PubMed] [Google Scholar]
  13. Gooding L. R., O'Connell K. A. Recognition by cytotoxic T lymphocytes of cells expressing fragments of the SV40 tumor antigen. J Immunol. 1983 Nov;131(5):2580–2586. [PubMed] [Google Scholar]
  14. Harlow E., Crawford L. V., Pim D. C., Williamson N. M. Monoclonal antibodies specific for simian virus 40 tumor antigens. J Virol. 1981 Sep;39(3):861–869. doi: 10.1128/jvi.39.3.861-869.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hirayama A., Takagaki Y., Karush F. Interaction of monoclonal anti-peptide antibodies with lysozyme. J Immunol. 1985 May;134(5):3241–3247. [PubMed] [Google Scholar]
  16. Katona I. M., Urban J. F., Jr, Scher I., Kanellopoulos-Langevin C., Finkelman F. D. Induction of an IgE response in mice by Nippostrongylus brasiliensis: characterization of lymphoid cells with intracytoplasmic or surface IgE. J Immunol. 1983 Jan;130(1):350–356. [PubMed] [Google Scholar]
  17. Katz D. H., Skidmore B. J., Katz L. R., Bogowitz C. A. Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host. J Exp Med. 1978 Sep 1;148(3):727–745. doi: 10.1084/jem.148.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klinman N. R., Pickard A. R., Sigal N. H., Gearhart P. J., Metcalf E. S., Pierce S. K. Assessing B cell diversification by antigen receptor and precursor cell analysis. Ann Immunol (Paris) 1976 Jun-Jul;127(3-4):489–502. [PubMed] [Google Scholar]
  19. Klinman N. R., Stone M. R. Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire. J Exp Med. 1983 Dec 1;158(6):1948–1961. doi: 10.1084/jem.158.6.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Knowles B. B., Koncar M., Pfizenmaier K., Solter D., Aden D. P., Trinchieri G. Genetic control of the cytotoxic T cell response to SV40 tumor-associated specific antigen. J Immunol. 1979 May;122(5):1798–1806. [PubMed] [Google Scholar]
  21. Levine A. J. Transformation-associated tumor antigens. Adv Cancer Res. 1982;37:75–109. doi: 10.1016/s0065-230x(08)60882-9. [DOI] [PubMed] [Google Scholar]
  22. Liu F. T., Bohn J. W., Ferry E. L., Yamamoto H., Molinaro C. A., Sherman L. A., Klinman N. R., Katz D. H. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980 Jun;124(6):2728–2737. [PubMed] [Google Scholar]
  23. Matzinger P. A one-receptor view of T-cell behaviour. Nature. 1981 Aug 6;292(5823):497–501. doi: 10.1038/292497a0. [DOI] [PubMed] [Google Scholar]
  24. Nisbet-Brown E., Singh B., Diener E. Antigen recognition. V. Requirement for histocompatibility between antigen-presenting cell and B cell in the response to a thymus-dependent antigen, and lack of allogeneic restriction between T and B cells. J Exp Med. 1981 Sep 1;154(3):676–687. doi: 10.1084/jem.154.3.676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pan S., Wettstein P. J., Knowles B. B. H-2Kb mutations limit the CTL response to SV40 TASA. J Immunol. 1982 Jan;128(1):243–246. [PubMed] [Google Scholar]
  26. Pfizenmaier K., Pan S. H., Knowles B. B. Preferential H-2 association in cytotoxic T cell responses to SV40 tumor-associated specific antigens. J Immunol. 1980 Apr;124(4):1888–1891. [PubMed] [Google Scholar]
  27. Pierce S. K., Klinman N. R. Antibody-specific immunoregulation. J Exp Med. 1977 Aug 1;146(2):509–519. doi: 10.1084/jem.146.2.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Riley R. L., Wylie D. E., Klinman N. R. B cell repertoire diversification precedes immunoglobulin receptor expression. J Exp Med. 1983 Nov 1;158(5):1733–1738. doi: 10.1084/jem.158.5.1733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rock K. L., Benacerraf B. Selective modification of a private I-A allo-stimulating determinant(s) upon association of antigen with an antigen-presenting cell. J Exp Med. 1984 Apr 1;159(4):1238–1252. doi: 10.1084/jem.159.4.1238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schmitt-Verhulst A. M., Shearer G. M. Bifunctional major histocompatibility-linked genetic regulation of cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes. J Exp Med. 1975 Oct 1;142(4):914–927. doi: 10.1084/jem.142.4.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sherman L. A. Recognition of conformational determinants on H-2 by cytolytic T lymphocytes. Nature. 1982 Jun 10;297(5866):511–513. doi: 10.1038/297511a0. [DOI] [PubMed] [Google Scholar]
  32. Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
  33. Singer A., Hodes R. J. Major histocompatibility complex-restricted self-recognition in responses to trinitrophenyl-ficoll. Adaptive differentiation and self-recognition by B cells. J Exp Med. 1982 Nov 1;156(5):1415–1434. doi: 10.1084/jem.156.5.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Soule H. R., Butel J. S. Subcellular Localization of simian virus 40 large tumor antigen. J Virol. 1979 May;30(2):523–532. doi: 10.1128/jvi.30.2.523-532.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tainer J. A., Getzoff E. D., Paterson Y., Olson A. J., Lerner R. A. The atomic mobility component of protein antigenicity. Annu Rev Immunol. 1985;3:501–535. doi: 10.1146/annurev.iy.03.040185.002441. [DOI] [PubMed] [Google Scholar]
  36. Tevethia S. S., Greenfield R. S., Flyer D. C., Tevethia M. J. SV40 transplantation antigen: relationship to SV40-specific proteins. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):235–242. doi: 10.1101/sqb.1980.044.01.027. [DOI] [PubMed] [Google Scholar]
  37. Walker S. M., Meinke G. C., Weigle W. O. Separation of various B-cell subpopulations from mouse spleen. I. Depletion of B cells by rosetting with glutaraldehyde-fixed, anti-immunoglobulin-coupled red blood cells. Cell Immunol. 1979 Aug;46(1):158–169. doi: 10.1016/0008-8749(79)90253-3. [DOI] [PubMed] [Google Scholar]
  38. Wylie D. E., Klinman N. R. The murine B cell repertoire responsive to an influenza-infected syngeneic cell line. J Immunol. 1981 Jul;127(1):194–198. [PubMed] [Google Scholar]
  39. Wylie D. E., Sherman L. A., Klinman N. R. Participation of the major histocompatibility complex in antibody recognition of viral antigens expressed on infected cells. J Exp Med. 1982 Feb 1;155(2):403–414. doi: 10.1084/jem.155.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zharhary D., Klinman N. R. Antigen responsiveness of the mature and generative B cell populations of aged mice. J Exp Med. 1983 Apr 1;157(4):1300–1308. doi: 10.1084/jem.157.4.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]
  43. Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]
  44. van Leeuwen A., Goulmy E., van Rood J. J. Major histocompatibility complex-restricted antibody reactivity mainly, but not exclusively, directed against cells from male donors. J Exp Med. 1979 Nov 1;150(5):1075–1083. doi: 10.1084/jem.150.5.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]

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