Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Aug;81(16):5204–5208. doi: 10.1073/pnas.81.16.5204

A molecular hybrid of the H-2Dd and H-2Ld genes expressed in the dm1 mutant.

S S Burnside, P Hunt, K Ozato, D W Sears
PMCID: PMC391666  PMID: 6206494

Abstract

Sequential immunoprecipitates show that H-2dm1 mutant cells express a hybrid "H-2D/L" antigen exhibiting determinants normally associated with two different gene products of the parental d haplotype-i.e., the H-2Dd and H-2Ld antigens. The hybrid H-2D/Ldm1 antigen appears to consist of a portion of the NH2-terminal extracellular half of the H-2Dd antigen "fused" to a portion of the COOH-terminal extracellular half of the H-2Ld antigen. This structure is inferred from the reactivity of dm1 antigens with cytotoxic T lymphocytes specific for H-2Ld determinants and with monoclonal antibodies specific for determinants in the structural domains of H-2Ld or H-2Dd. The H-2D/Ldm1 molecule apparently retains all of the third external domain (C2 or alpha 3) and part of the second external domain (C1 or alpha 2) of H-2Ld, but its first external domain (N or alpha 1) derives from H-2Dd. From these findings and from previous peptide mapping studies, we propose that the H-2D/Ldm1 antigen is the product of a hybrid gene that has resulted from an unequal crossover between the parental H-2Dd and H-2Ld genes, leaving the N exon and part of the C1 exon of the H-2Dd gene joined to the H-2Ld gene beginning somewhere within its C1 exon.

Full text

PDF
5207

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown J. L., Nairen R., Natherson S. G. Structural differences between the mouse H-2D products of the mutant B10.D2.M504 (H-2da) and the parental nonmutant strain B10.D2 (H-2d). J Immunol. 1978 Mar;120(3):726–733. [PubMed] [Google Scholar]
  2. Ciavarra R., Forman J. H-2L-restricted recognition of viral antigens In the H-2d haplotype, anti-vesicular stomatitis virus cytotoxic T cells are restricted solely by H-2L. J Exp Med. 1982 Sep 1;156(3):778–790. doi: 10.1084/jem.156.3.778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coligan J. E., Kindt T. J., Uehara H., Martinko J., Nathenson S. G. Primary structure of a murine transplantation antigen. Nature. 1981 May 7;291(5810):35–39. doi: 10.1038/291035a0. [DOI] [PubMed] [Google Scholar]
  4. Ehrlich P. H., Moyle W. R., Moustafa Z. A., Canfield R. E. Mixing two monoclonal antibodies yields enhanced affinity for antigen. J Immunol. 1982 Jun;128(6):2709–2713. [PubMed] [Google Scholar]
  5. Evans G. A., Margulies D. H., Camerini-Otero R. D., Ozato K., Seidman J. G. Structure and expression of a mouse major histocompatibility antigen gene, H-2Ld. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1994–1998. doi: 10.1073/pnas.79.6.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans G. A., Margulies D. H., Shykind B., Seidman J. G., Ozato K. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens. Nature. 1982 Dec 23;300(5894):755–757. doi: 10.1038/300755a0. [DOI] [PubMed] [Google Scholar]
  7. Flavell R. A., Kooter J. M., De Boer E., Little P. F., Williamson R. Analysis of the beta-delta-globin gene loci in normal and Hb Lepore DNA: direct determination of gene linkage and intergene distance. Cell. 1978 Sep;15(1):25–41. doi: 10.1016/0092-8674(78)90080-6. [DOI] [PubMed] [Google Scholar]
  8. Hansen T. H., Cullen S. E., Melvold R., Kohn H., Flaherty L., Sachs D. H. Mutation in a new H-2-associated histocompatibility gene closely linked to H-2D. J Exp Med. 1977 Jun 1;145(6):1550–1558. doi: 10.1084/jem.145.6.1550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hansen T. H., Ozato K., Melino M. R., Coligan J. E., Kindt T. J., Jandinski J. J., Sachs D. H. Immunochemical evidence in two haplotypes for at least three D region-encoded molecules, D, L, and R. J Immunol. 1981 May;126(5):1713–1716. [PubMed] [Google Scholar]
  10. Hansen T. H., Ozato K., Sachs D. H. Heterogeneity of H-2D region associated genes and gene products. Adv Immunol. 1983;34:39–70. doi: 10.1016/s0065-2776(08)60376-4. [DOI] [PubMed] [Google Scholar]
  11. Hogarth P. M., Walker I. D., Rigby A. J., McKenzie I. F. The H-2dm1 mutation and Qa antigens. Immunogenetics. 1983;18(6):617–624. doi: 10.1007/BF00345969. [DOI] [PubMed] [Google Scholar]
  12. Hood L., Steinmetz M., Malissen B. Genes of the major histocompatibility complex of the mouse. Annu Rev Immunol. 1983;1:529–568. doi: 10.1146/annurev.iy.01.040183.002525. [DOI] [PubMed] [Google Scholar]
  13. Hunt P., Sears D. W. CTL cross-reactivities reveal shared immunodominant determinants created by structurally homologous regions of MHC class I antigens. J Immunol. 1983 Mar;130(3):1439–1446. [PubMed] [Google Scholar]
  14. Iványi D., Démant P. Molecular heterogeneity of D-end products detected by anti-H-2.28 sera. II. B10.D2(M504) (H-2dm1) mutant fails to express one of the two H-2.4-, 28 + Dd region molecules. Immunogenetics. 1982;15(5):467–476. doi: 10.1007/BF00345906. [DOI] [PubMed] [Google Scholar]
  15. Iványi D., Démant P. One (H-2D2b) of the three Db region-controlled molecules (H-2D1b, H-2D2b, H-2Lb) is not detected in bm13 mutant. J Immunol. 1983 Sep;131(3):1080–1084. [PubMed] [Google Scholar]
  16. Klein J. H-2 mutations: their genetics and effect on immune functions. Adv Immunol. 1978;26:55–146. doi: 10.1016/s0065-2776(08)60229-1. [DOI] [PubMed] [Google Scholar]
  17. Margulies D. H., Evans G. A., Ozato K., Camerini-Otero R. D., Tanaka K., Appella E., Seidman J. G. Expression of H-2Dd and H-2Ld mouse major histocompatibility antigen genes in L cells after DNA-mediated gene transfer. J Immunol. 1983 Jan;130(1):463–470. [PubMed] [Google Scholar]
  18. Mears J. G., Ramirez F., Leibowitz D., Bank A. Organization of human delta--and beta-globin genes in cellular DNA and the presence of intragenic inserts. Cell. 1978 Sep;15(1):15–23. doi: 10.1016/0092-8674(78)90079-x. [DOI] [PubMed] [Google Scholar]
  19. Melvold R. W., Stuart P. M., Busker A. E., Beck-Maier B. A new loss mutant in the H-2d haplotype. Transplant Proc. 1983 Dec;15(4):2045–2047. [PubMed] [Google Scholar]
  20. Moore K. W., Sher B. T., Sun Y. H., Eakle K. A., Hood L. DNA sequence of a gene encoding a BALB/c mouse Ld transplantation antigen. Science. 1982 Feb 5;215(4533):679–682. doi: 10.1126/science.7058332. [DOI] [PubMed] [Google Scholar]
  21. Nairn R., Nathenson S. G., Coligan J. E. Amino acid sequence of cyanogen bromide fragment CN-C (residues 24-98) of the mouse histocompatibility antigen H-2Dd. A comparison of the amino-terminal 100 residues of H-2Dd, Dd, Kd, and Kb reveals discrete areas of diversity. Biochemistry. 1981 Aug 4;20(16):4739–4745. doi: 10.1021/bi00519a033. [DOI] [PubMed] [Google Scholar]
  22. Nairn R., Yamaga K., Nathenson S. G. Biochemistry of the gene products from murine MHC mutants. Annu Rev Genet. 1980;14:241–277. doi: 10.1146/annurev.ge.14.120180.001325. [DOI] [PubMed] [Google Scholar]
  23. Ozato K., Evans G. A., Shykind B., Margulies D. H., Seidman J. G. Hybrid H-2 histocompatibility gene products assign domains recognized by alloreactive T cells. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2040–2043. doi: 10.1073/pnas.80.7.2040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Reiss C. S., Evans G. A., Margulies D. H., Seidman J. G., Burakoff S. J. Allospecific and virus-specific cytolytic T lymphocytes are restricted to the N or C1 domain of H-2 antigens expressed on L cells after DNA-mediated gene transfer. Proc Natl Acad Sci U S A. 1983 May;80(9):2709–2712. doi: 10.1073/pnas.80.9.2709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schulze D. H., Pease L. R., Geier S. S., Reyes A. A., Sarmiento L. A., Wallace R. B., Nathenson S. G. Comparison of the cloned H-2Kbm1 variant gene with the H-2Kb gene shows a cluster of seven nucleotide differences. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2007–2011. doi: 10.1073/pnas.80.7.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sears D. W., Wilson P. H. Biochemical evidence for structurally distinct H-2Dd antigens differing in serological properties. Immunogenetics. 1981;13(4):275–284. doi: 10.1007/BF00364493. [DOI] [PubMed] [Google Scholar]
  29. Sherman L. A., Randolph C. P. Monoclonal anti-H-2Kb antibodies detect serological differences between H-2Kb mutants. Immunogenetics. 1981;12(1-2):183–186. doi: 10.1007/BF01561661. [DOI] [PubMed] [Google Scholar]
  30. Weiss E. H., Mellor A., Golden L., Fahrner K., Simpson E., Hurst J., Flavell R. A. The structure of a mutant H-2 gene suggests that the generation of polymorphism in H-2 genes may occur by gene conversion-like events. Nature. 1983 Feb 24;301(5902):671–674. doi: 10.1038/301671a0. [DOI] [PubMed] [Google Scholar]
  31. Wilson P. H., Nairn R., Nathenson S. G., Sears D. W. Unexpected complexity of the dm1 mutation revealed in the structure of three H-2D/L-related antigens. Immunogenetics. 1982 Mar;15(3):225–237. doi: 10.1007/BF00364331. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES