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. 1981 Mar 1;153(3):501–513. doi: 10.1084/jem.153.3.501

Expression of hybrid Ia molecules on the cell surface of reticulum cell sarcomas that are undetectable on host SJL/J lymphocytes

SM Wilbur, B Bonavida
PMCID: PMC2186102  PMID: 6166700

Abstract

SJL/J (H-2 (8)) lymphocytes, primed in vitro against primary, cultured, and transplantable syngeneic reticulum cell sarcomas (RCS) were found to recognize and bind to the tumor without subsequent cytolysis. Additional data showed that the recognition was also directed against Ia molecules of the H-2(d), but not H-2(k), haplotype. Normal spleen cells of DBA/2, B 10.D2, and B 10.OL mice were bound, whereas those of CBA, B 10.BR, B 10.A, B 10.GD, and D2.GD were not. Furthermore, the Ia molecules were in the form of a hybrid, because spleen cells from F(1) progeny of a B10.A and a B10.GD parent were recognized and bound as effectively as the RCS. Recognition was not restricted solely to the H-2(d) haplotype. Spleen cells from B10.S(9R) mice were also significantly bound. This result suggested that the RCS expresses a hybrid Ia molecule containing a β-chain of the H-2(8) haplotype. Recognition of this hybrid Ia molecule by the host resulted in a cross- reactive recognition of H-2(d) specificities. Further analysis revealed that the RCS express on their cell surface an α-chain of the hybrid Ia molecule which is involved in host anti-tumor recognition. Preincubation of the RCS with monoclonal antibody directed against the Ia.7 specificity on the α-chain could block lymphocyte-to-tumor cell binding. The blocking activity could be removed by preabsorption of the antibody on the RCS, as well as normal Ia.7-bearing lymphocytes, but not on lymphocytes that do not express Ia.7, such as SJL/J. The data suggest that the hybrid Ia molecules expressed on the RCS, and recognized by tumor-primed syngeneic lymphocytes, are composed of both a syngeneic and an alien chain. The component alien to the SJL/J host is the Ia.7-bearing α-chain. Normal SJL/J cells synthesize but do not express the β-chain. In the RCS, however, alien α-chain synthesis permits expression of the syngeneic β-chain in the form of a hybrid Ia molecule.

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Selected References

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  1. Bonavida B., Roman J. M., Hutchinson I. V. Inappropriate alloantigen-like specificities detected on reticulum cell sarcomas of SJL/J mice: characterization and biologic role. Transplant Proc. 1980 Mar;12(1):59–64. [PubMed] [Google Scholar]
  2. Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cook R. G., Vitetta E. S., Uhr J. W., Capra J. D. Structural studies on the murine Ia alloantigens. V. Evidence that the structural gene for the I-E/C beta polypeptide is encoded within the I-A subregion. J Exp Med. 1979 Apr 1;149(4):981–986. doi: 10.1084/jem.149.4.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cullen S. E., Freed J. H., Nathenson S. G. Structural and serological properties of murine Ia alloantigens. Transplant Rev. 1976;30:236–270. doi: 10.1111/j.1600-065x.1976.tb00222.x. [DOI] [PubMed] [Google Scholar]
  5. David C. S., Cullen S. E. Murine Ia antigens: identification and mapping of Ia.23 and further definition of the I-E subregion. J Immunol. 1978 May;120(5):1659–1662. [PubMed] [Google Scholar]
  6. Dorf M. E., Benacerraf B. Complementation of H-2-linked Ir genes in the mouse. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3671–3675. doi: 10.1073/pnas.72.9.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jones P. P., Murphy D. B., McDevitt H. O. Two-gene control of the expression of a murine Ia antigen. J Exp Med. 1978 Oct 1;148(4):925–939. doi: 10.1084/jem.148.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Katz I. R., Lerman S. P., Ponzio N. M., Shreffler D. C., Thorbecke G. J. Growth of SJL/J-derived transplantable reticulum cell sarcoma as related to its ability to induce T-cell proliferation in the host. I. Dominant negative genetic influences of other parent haplotype in F1 hybrids of SJL/J mice. J Exp Med. 1980 Feb 1;151(2):347–361. doi: 10.1084/jem.151.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lafuse W. P., McCormick J. F., David C. S. Serological and biochemical identification of hybrid Ia antigens. J Exp Med. 1980 Mar 1;151(3):709–715. doi: 10.1084/jem.151.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lerman S. P., Chapman-Alexander J., Umetsu D., Thorbecke G. J. Properties of reticulum cell sarcomas in SJL/J mice. VII. Nature of normal lymphoid cells proliferating in response to tumor cells. Cell Immunol. 1979 Mar 1;43(1):209–213. doi: 10.1016/0008-8749(79)90165-5. [DOI] [PubMed] [Google Scholar]
  11. Lerman S. P., Chapman J. M., Carswell E. A., Thorbecke G. J. Properties of reticulum-cell sarcomas in SJL/J mice. I. Proliferative response to tumor cells of T-derived lymphoid cells from normal mice. Int J Cancer. 1974 Dec 15;14(6):808–816. doi: 10.1002/ijc.2910140615. [DOI] [PubMed] [Google Scholar]
  12. Lipscomb M. F., Ben-Sasson S. Z., Uhr J. W. Specific binding of T lymphocytes to macrophages. I. Kinetics of binding. J Immunol. 1977 May;118(5):1748–1754. [PubMed] [Google Scholar]
  13. Lipsky P. E., Rosenthal A. S. Macrophage-lymphocyte interaction. II. Antigen-mediated physical interactions between immune guinea pig lymph node lymphocytes and syngeneic macrophages. J Exp Med. 1975 Jan 1;141(1):138–154. doi: 10.1084/jem.141.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lozner E. C., Sachs D. H., Shearer G. M., Terry W. D. B-cell alloantigens determined by the H-2 linked Ir region are associated with mixed lymphocyte culture stimulation. Science. 1974 Feb 22;183(4126):757–759. doi: 10.1126/science.183.4126.757. [DOI] [PubMed] [Google Scholar]
  15. Lyons C. R., Tucker T. F., Uhr J. W. Specific binding of T lymphocytes to macrophages. V. The role of Ia antigens on Mphi in the binding. J Immunol. 1979 Apr;122(4):1598–1600. [PubMed] [Google Scholar]
  16. Martz E. Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. I. Resolution and characterization. J Immunol. 1975 Jul;115(1):261–267. [PubMed] [Google Scholar]
  17. Nagy Z., Elliott B. E., Nabholz M. Specific binding of K- and I-region products of the H-2 complex to activated thymus-derived (T) cells belonging to different Ly subclasses. J Exp Med. 1976 Dec 1;144(6):1545–1553. doi: 10.1084/jem.144.6.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nichols E. A., Ruddle F. H. A review of enzyme polymorphism, linkage and electrophoretic conditions for mouse and somatic cell hybrids in starch gels. J Histochem Cytochem. 1973 Dec;21(12):1066–1081. doi: 10.1177/21.12.1066. [DOI] [PubMed] [Google Scholar]
  19. Nichols E. A., Ruddle F. H. Polymorphism and linkage of glutathione reductase in Mus musculus. Biochem Genet. 1975 Jun;13(5-6):323–329. doi: 10.1007/BF00485817. [DOI] [PubMed] [Google Scholar]
  20. Ozato K., Lunney J. K., El-Gamil M., Sachs D. H. Evidence for the absence of I-E/C antigen expression on the cell surface in mice of the H-2b or H-2s haplotypes. J Immunol. 1980 Aug;125(2):940–945. [PubMed] [Google Scholar]
  21. Ponzio N. M., David C. S., Shreffler D. C., Thorbecke G. J. Properties of reticulum cell sarcomas in SJL/J mice. V. Nature of reticulum cell sarcoma surface antigen which induces proliferation of normal SJL/J T cells. J Exp Med. 1977 Jul 1;146(1):132–145. doi: 10.1084/jem.146.1.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roman J. M., Bonavida B. Inappropriate alloantigen-like specificities detected on spontaneous and transplantable reticulum cell sarcomas of SJL/J mice. J Immunogenet. 1980 Feb;7(1):61–70. doi: 10.1111/j.1744-313x.1980.tb00708.x. [DOI] [PubMed] [Google Scholar]
  23. Schwartz R. H., Dorf M. E., Benacerraf B., Paul W. E. The requirement for two complementing Ir-GLphi immune response genes in the T-lymphocyte proliferative response to poly-(Glu53Lys36Phe11). J Exp Med. 1976 Apr 1;143(4):897–905. doi: 10.1084/jem.143.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shiku H., Kisielow P., Bean M. A., Takahashi T., Boyse E. A., Oettgen H. F., Old L. J. Expression of T-cell differentiation antigens on effector cells in cell-mediated cytotoxicity in vitro. Evidence for functional heterogeneity related to the surface phenotype of T cells. J Exp Med. 1975 Jan 1;141(1):227–241. doi: 10.1084/jem.141.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ziegler K., Unanue E. R. The specific binding of Listeria monocytogenes-immune T lymphocytes to macrophages. I. Quantitation and role of H-2 gene products. J Exp Med. 1979 Nov 1;150(5):1143–1160. doi: 10.1084/jem.150.5.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]

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