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. 1989 Mar 1;169(3):1043–1058. doi: 10.1084/jem.169.3.1043

The tumor-rejection antigens of the 1591 ultraviolet fibrosarcoma. Potential origin and evolutionary implications

PMCID: PMC2189265  PMID: 2564413

Abstract

Previously, we cloned and sequenced the three novel MHC class I genes expressed by the C3H UV fibrosarcoma, 1591. We have extended the analysis of the polymorphic nature of these genes relative to the C3H strain. Scattered nucleotide differences among the tumor genes as compared with the C3H H-2 and Qa sequences make it highly unlikely that the novel tumor genes were generated by recombination between endogenous C3H sequences. Given that two of the tumor clones, A149 and A166, are remarkably similar in amino acid and DNA sequence to H-2Lq and H-2Dq, respectively, we also examined the 1591 RP2 and GUS loci for evidence of polymorphism. Compared with C3H and B10.AKM, 1591 appears to be heterozygous at each of these loci, consistent with an H-2q origin for the two novel 1591 class I genes. Interestingly, the third tumor gene, designated A216, shares certain characteristics with the H- 2Ks antigen, reminiscent of the naturally occurring combination of H- 2Ks, H-2Dq, and H-2Lq antigens found in some Swiss mouse strains. As a result, we propose that the non-C3H/HeN characteristics displayed by the 1591 tumor point to a non-C3H origin for the novel tumor class I genes of 1591.

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Selected References

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  1. Basombrío M. A., Prehn R. T. Studies on the basis for diversity and time of appearance of antigens in chemically induced tumors. Natl Cancer Inst Monogr. 1972 Dec;35:117–124. [PubMed] [Google Scholar]
  2. Basombrío M. A. Search for common antigenicities among twenty-five sarcomas induced by methylcholanthrene. Cancer Res. 1970 Oct;30(10):2458–2462. [PubMed] [Google Scholar]
  3. Brégégère F. A directional process of gene conversion is expected to yield dynamic polymorphism associated with stability of alternative alleles in class I histocompatibility antigens gene family. Biochimie. 1983 Apr-May;65(4-5):229–237. doi: 10.1016/s0300-9084(83)80274-0. [DOI] [PubMed] [Google Scholar]
  4. Chen Y. T., Obata Y., Stockert E., Old L. J. Thymus-leukemia (TL) antigens of the mouse. Analysis of TL mRNA and TL cDNA TL+ and TL- strains. J Exp Med. 1985 Oct 1;162(4):1134–1148. doi: 10.1084/jem.162.4.1134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Daynes R. A., Spellman C. W., Woodward J. G., Stewart D. A. Studies into the transplantation biology of ultraviolet light-induced tumors. Transplantation. 1977 Apr;23(4):343–348. doi: 10.1097/00007890-197704000-00008. [DOI] [PubMed] [Google Scholar]
  6. De Plaen E., Lurquin C., Van Pel A., Mariamé B., Szikora J. P., Wölfel T., Sibille C., Chomez P., Boon T. Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of tum- antigen P91A and identification of the tum- mutation. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2274–2278. doi: 10.1073/pnas.85.7.2274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DuBois G. C., Law L. W. Biochemical characterization and biologic activities of 82- and 86-kDa tumor antigens isolated from a methylcholanthrene-induced sarcoma, CII-7. Int J Cancer. 1986 Jun 15;37(6):925–931. doi: 10.1002/ijc.2910370620. [DOI] [PubMed] [Google Scholar]
  8. Egorov I. K., Egorov O. S. Detection of new MHC mutations in mice by skin grafting, tumor transplantation and monoclonal antibodies: a comparison. Genetics. 1988 Feb;118(2):287–298. doi: 10.1093/genetics/118.2.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Elliott R. W., Berger F. G. DNA sequence polymorphism in an androgen-regulated gene is associated with alteration in the encoded RNAs. Proc Natl Acad Sci U S A. 1983 Jan;80(2):501–504. doi: 10.1073/pnas.80.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FOLEY E. J. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res. 1953 Dec;13(12):835–837. [PubMed] [Google Scholar]
  11. Fisher D. A., Hunt S. W., 3rd, Hood L. Structure of a gene encoding a murine thymus leukemia antigen, and organization of Tla genes in the BALB/c mouse. J Exp Med. 1985 Aug 1;162(2):528–545. doi: 10.1084/jem.162.2.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fisher M. S., Kripke M. L. Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice. Science. 1982 Jun 4;216(4550):1133–1134. doi: 10.1126/science.6210958. [DOI] [PubMed] [Google Scholar]
  13. Fisher M. S., Kripke M. L. Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1688–1692. doi: 10.1073/pnas.74.4.1688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hostetler L. W., Ananthaswamy H. N., Kripke M. L. Generation of tumor-specific transplantation antigens by UV radiation can occur independently of neoplastic transformation. J Immunol. 1986 Oct 15;137(8):2721–2725. [PubMed] [Google Scholar]
  15. KLEIN G., SJOGREN H. O., KLEIN E., HELLSTROM K. E. Demonstration of resistance against methylcholanthrene-induced sarcomas in the primary autochthonous host. Cancer Res. 1960 Dec;20:1561–1572. [PubMed] [Google Scholar]
  16. Klein J., Figueroa F., David C. S. H-2 haplotypes, genes and antigens: second listing. II. The H-2 complex. Immunogenetics. 1983;17(6):553–596. doi: 10.1007/BF00366126. [DOI] [PubMed] [Google Scholar]
  17. Kourilsky P., Chaouat G., Rabourdin-Combe C., Claverie J. M. Working principles in the immune system implied by the "peptidic self" model. Proc Natl Acad Sci U S A. 1987 May;84(10):3400–3404. doi: 10.1073/pnas.84.10.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kripke M. L. Antigenicity of murine skin tumors induced by ultraviolet light. J Natl Cancer Inst. 1974 Nov;53(5):1333–1336. doi: 10.1093/jnci/53.5.1333. [DOI] [PubMed] [Google Scholar]
  19. Kripke M. L., Fisher M. S. Immunologic parameters of ultraviolet carcinogenesis. J Natl Cancer Inst. 1976 Jul;57(1):211–215. doi: 10.1093/jnci/57.1.211. [DOI] [PubMed] [Google Scholar]
  20. Kripke M. L. Immunologic mechanisms in UV radiation carcinogenesis. Adv Cancer Res. 1981;34:69–106. doi: 10.1016/s0065-230x(08)60239-0. [DOI] [PubMed] [Google Scholar]
  21. Kvist S., Roberts L., Dobberstein B. Mouse histocompatibility genes: structure and organisation of a Kd gene. EMBO J. 1983;2(2):245–254. doi: 10.1002/j.1460-2075.1983.tb01413.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Law L. W. Characteristics of tumour-specific antigens. Cancer Surv. 1985;4(1):3–19. [PubMed] [Google Scholar]
  23. Lee D. R., Rubocki R. J., Lie W. R., Hansen T. H. The murine MHC class I genes, H-2Dq and H-2Lq, are strikingly homologous to each other, H-2Ld, and two genes reported to encode tumor-specific antigens. J Exp Med. 1988 Nov 1;168(5):1719–1739. doi: 10.1084/jem.168.5.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lillehoj E. P., Hansen T. H., Sachs D. H., Coligan J. E. Primary structural evidence that the H-2Dq region encodes at least three distinct gene products: Dq, Lq, and Rq. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2499–2503. doi: 10.1073/pnas.81.8.2499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Linsk R., Vogel J., Stauss H., Forman J., Goodenow R. S. Structure and function of three novel MHC class I antigens derived from a C3H ultraviolet-induced fibrosarcoma. J Exp Med. 1986 Sep 1;164(3):794–813. doi: 10.1084/jem.164.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Martinko J. M., Solheim J. C., Geliebter J. The H-2Kkml mutation: nucleotide sequence and comparative analysis. Mol Immunol. 1987 Feb;24(2):197–200. doi: 10.1016/0161-5890(87)90092-7. [DOI] [PubMed] [Google Scholar]
  27. McMillan M., Lewis K. D., Rovner D. M. Molecular characterization of novel H-2 class I molecules expressed by a C3H UV-induced fibrosarcoma. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5485–5489. doi: 10.1073/pnas.82.16.5485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miyada C. G., Klofelt C., Reyes A. A., McLaughlin-Taylor E., Wallace R. B. Evidence that polymorphism in the murine major histocompatibility complex may be generated by the assortment of subgene sequences. Proc Natl Acad Sci U S A. 1985 May;82(9):2890–2894. doi: 10.1073/pnas.82.9.2890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nathenson S. G., Geliebter J., Pfaffenbach G. M., Zeff R. A. Murine major histocompatibility complex class-I mutants: molecular analysis and structure-function implications. Annu Rev Immunol. 1986;4:471–502. doi: 10.1146/annurev.iy.04.040186.002351. [DOI] [PubMed] [Google Scholar]
  30. Obata Y., Chen Y. T., Stockert E., Old L. J. Structural analysis of TL genes of the mouse. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5475–5479. doi: 10.1073/pnas.82.16.5475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ozato K., Hansen T. H., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. II. Antibodies to the H-2Ld antigen, the products of a third polymorphic locus of the mouse major histocompatibility complex. J Immunol. 1980 Dec;125(6):2473–2477. [PubMed] [Google Scholar]
  32. Ozato K., Mayer N. M., Sachs D. H. Monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation. 1982 Sep;34(3):113–120. doi: 10.1097/00007890-198209000-00001. [DOI] [PubMed] [Google Scholar]
  33. Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
  34. PREHN R. T., MAIN J. M. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957 Jun;18(6):769–778. [PubMed] [Google Scholar]
  35. Paigen K., Swank R. T., Tomino S., Ganschow R. E. The molecular genetics of mammalian glucuronidase. J Cell Physiol. 1975 Apr;85(2 Pt 2 Suppl 1):379–392. doi: 10.1002/jcp.1040850406. [DOI] [PubMed] [Google Scholar]
  36. Pease L. R. Diversity in H-2 genes encoding antigen-presenting molecules is generated by interactions between members of the major histocompatibility complex gene family. Transplantation. 1985 Mar;39(3):227–231. doi: 10.1097/00007890-198503000-00001. [DOI] [PubMed] [Google Scholar]
  37. Philipps C., McMillan M., Flood P. M., Murphy D. B., Forman J., Lancki D., Womack J. E., Goodenow R. S., Schreiber H. Identification of a unique tumor-specific antigen as a novel class I major histocompatibility molecule. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5140–5144. doi: 10.1073/pnas.82.15.5140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rice M. C., O'Brien S. J. Genetic variance of laboratory outbred Swiss mice. Nature. 1980 Jan 10;283(5743):157–161. doi: 10.1038/283157a0. [DOI] [PubMed] [Google Scholar]
  39. Roberts L. K. Characterization of a cloned ultraviolet radiation (UV)-induced suppressor T cell line that is capable of inhibiting anti-UV tumor-immune responses. J Immunol. 1986 Mar 1;136(5):1908–1916. [PubMed] [Google Scholar]
  40. Rogers M. J., Siwarski D. F., Shacter E., Maloy W. L., Lillehoj E. P., Coligan J. E. Three distinct H-2Ks molecules differing at the carboxy terminus are expressed on a tumor from SJL/J mice. J Immunol. 1986 Nov 1;137(9):3006–3012. [PubMed] [Google Scholar]
  41. Schepart B. S., Takahashi H., Cozad K. M., Murray R., Ozato K., Appella E., Frelinger J. A. The nucleotide sequence and comparative analysis of the H-2Dp class I H-2 gene. J Immunol. 1986 May 1;136(9):3489–3495. [PubMed] [Google Scholar]
  42. Schreiber H., Ward P. L., Rowley D. A., Stauss H. J. Unique tumor-specific antigens. Annu Rev Immunol. 1988;6:465–483. doi: 10.1146/annurev.iy.06.040188.002341. [DOI] [PubMed] [Google Scholar]
  43. Sher B. T., Nairn R., Coligan J. E., Hood L. E. DNA sequence of the mouse H-2Dd transplantation antigen gene. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1175–1179. doi: 10.1073/pnas.82.4.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Song E. S., Linsk R., Olson C. A., McMillan M., Goodenow R. S. Allospecific cytotoxic T lymphocytes recognize an H-2 peptide in the context of a murine major histocompatibility complex class I molecule. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1927–1931. doi: 10.1073/pnas.85.6.1927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Srivastava P. K., Chen Y. T., Old L. J. 5'-structural analysis of genes encoding polymorphic antigens of chemically induced tumors. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3807–3811. doi: 10.1073/pnas.84.11.3807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Srivastava P. K., DeLeo A. B., Old L. J. Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc Natl Acad Sci U S A. 1986 May;83(10):3407–3411. doi: 10.1073/pnas.83.10.3407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Stauss H. J., Linsk R., Fischer A., Watts S., Banasiak D., Haberman A., Clark I., Forman J., McMillan M., Schreiber H. Isolation of the MHC genes encoding the tumour-specific class I antigens expressed on a murine fibrosarcoma. J Immunogenet. 1986 Apr-Jun;13(2-3):101–111. doi: 10.1111/j.1744-313x.1986.tb01090.x. [DOI] [PubMed] [Google Scholar]
  48. Stauss H. J., Van Waes C., Fink M. A., Starr B., Schreiber H. Identification of a unique tumor antigen as rejection antigen by molecular cloning and gene transfer. J Exp Med. 1986 Nov 1;164(5):1516–1530. doi: 10.1084/jem.164.5.1516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Stephan D., Sun H., Lindahl K. F., Meyer E., Hämmerling G., Hood L., Steinmetz M. Organization and evolution of D region class I genes in the mouse major histocompatibility complex. J Exp Med. 1986 May 1;163(5):1227–1244. doi: 10.1084/jem.163.5.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Ullrich S. E., Kripke M. L. Mechanisms in the suppression of tumor rejection produced in mice by repeated UV irradiation. J Immunol. 1984 Nov;133(5):2786–2790. [PubMed] [Google Scholar]
  51. Ullrich S. J., Robinson E. A., Law L. W., Willingham M., Appella E. A mouse tumor-specific transplantation antigen is a heat shock-related protein. Proc Natl Acad Sci U S A. 1986 May;83(10):3121–3125. doi: 10.1073/pnas.83.10.3121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Urban J. L., Holland J. M., Kripke M. L., Schreiber H. Immunoselection of tumor cell variants by mice suppressed with ultraviolet radiation. J Exp Med. 1982 Oct 1;156(4):1025–1041. doi: 10.1084/jem.156.4.1025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Urban J. L., Kripke M. L., Schreiber H. Stepwise immunologic selection of antigenic variants during tumor growth. J Immunol. 1986 Nov 1;137(9):3036–3041. [PubMed] [Google Scholar]
  54. Vogel J. M., Davis A. C., McKinney D. M., McMillan M., Martin W. J., Goodenow R. S. Molecular characterization of the C3HfB/HeN H-2Kkm2 mutation. Implications for the molecular basis of alloreactivity. J Exp Med. 1988 Nov 1;168(5):1781–1800. doi: 10.1084/jem.168.5.1781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Watts S., Vogel J. M., Harriman W. D., Itoh T., Stauss H. J., Goodenow R. S. DNA sequence analysis of the C3H H-2Kk and H-2Dk loci. Evolutionary relationships to H-2 genes from four other mouse strains. J Immunol. 1987 Dec 1;139(11):3878–3885. [PubMed] [Google Scholar]
  56. Weiss E., Golden L., Zakut R., Mellor A., Fahrner K., Kvist S., Flavell R. A. The DNA sequence of the H-2kb gene: evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibilty antigens. EMBO J. 1983;2(3):453–462. doi: 10.1002/j.1460-2075.1983.tb01444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Wortzel R. D., Philipps C., Schreiber H. Multiple tumour-specific antigens expressed on a single tumour cell. Nature. 1983 Jul 14;304(5922):165–167. doi: 10.1038/304165a0. [DOI] [PubMed] [Google Scholar]
  58. Wortzel R. D., Urban J. L., Schreiber H. Malignant growth in the normal host after variant selection in vitro with cytolytic T-cell lines. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2186–2190. doi: 10.1073/pnas.81.7.2186. [DOI] [PMC free article] [PubMed] [Google Scholar]

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