Skip to main content
NCBI home page
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
. 1987 Jan;84(1):209–213. doi: 10.1073/pnas.84.1.209

Evolutionary and genetic implications of sequence variation in two nonallelic HLA-DR beta-chain cDNA sequences.

J M Curtsinger, J M Hilden, J S Cairns, F H Bach
PMCID: PMC304172  PMID: 3467350

Abstract

Most HLA haplotypes carry two expressed DR beta-chain genes; in the DR4 haplotype, the polymorphic locus has been called DR beta 1 and the apparently nonpolymorphic locus has been called DR beta 2. We have isolated nearly full-length DR beta-chain cDNA clones representing each of these two loci from a cell line homozygous for DR4 and Dw4. The clones have been sequenced and the sequences compared with published DR beta cDNA sequences derived from other haplotypes. A comparison of our sequences with other published cDNA sequences did not allow assignment of these other sequences to either the beta 1 or beta 2 locus. Comparison of our DR4 beta 1 sequence with DR beta 1 sequences isolated from other DR4-positive cells suggests that the alleles of DR4 beta 1 may have recently diverged from a common ancestor. The apparent lack of polymorphism of DR beta 2 may in part be a reflection of this recent divergence.

Full text

PDF
209

Selected References

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

  1. Auffray C., Strominger J. L. Molecular genetics of the human major histocompatibility complex. Adv Hum Genet. 1986;15:197–247. doi: 10.1007/978-1-4615-8356-1_4. [DOI] [PubMed] [Google Scholar]
  2. Bach F. H., Watson A. J. Dw/LD associated molecular polymorphism of DR4 beta-chains: intramolecular localization of polymorphic sites. J Immunol. 1983 Oct;131(4):1622–1625. [PubMed] [Google Scholar]
  3. Bell J. I., Denny D. W., Jr, McDevitt H. O. Structure and polymorphism of murine and human class II major histocompatibility antigens. Immunol Rev. 1985 Jul;84:51–71. doi: 10.1111/j.1600-065x.1985.tb01125.x. [DOI] [PubMed] [Google Scholar]
  4. Bell J. I., Estess P., St John T., Saiki R., Watling D. L., Erlich H. A., McDevitt H. O. DNA sequence and characterization of human class II major histocompatibility complex beta chains from the DR1 haplotype. Proc Natl Acad Sci U S A. 1985 May;82(10):3405–3409. doi: 10.1073/pnas.82.10.3405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cairns J. S., Curtsinger J. M., Dahl C. A., Freeman S., Alter B. J., Bach F. H. Sequence polymorphism of HLA DR beta 1 alleles relating to T-cell-recognized determinants. Nature. 1985 Sep 12;317(6033):166–168. doi: 10.1038/317166a0. [DOI] [PubMed] [Google Scholar]
  6. Dale R. M., McClure B. A., Houchins J. P. A rapid single-stranded cloning strategy for producing a sequential series of overlapping clones for use in DNA sequencing: application to sequencing the corn mitochondrial 18 S rDNA. Plasmid. 1985 Jan;13(1):31–40. doi: 10.1016/0147-619x(85)90053-8. [DOI] [PubMed] [Google Scholar]
  7. Denaro M., Hammerling U., Rask L., Peterson P. A. The Eb beta gene may have acted as the donor gene in a gene conversion-like event generating the Abm 12 beta mutant. EMBO J. 1984 Sep;3(9):2029–2032. doi: 10.1002/j.1460-2075.1984.tb02086.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gregersen P. K., Shen M., Song Q. L., Merryman P., Degar S., Seki T., Maccari J., Goldberg D., Murphy H., Schwenzer J. Molecular diversity of HLA-DR4 haplotypes. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2642–2646. doi: 10.1073/pnas.83.8.2642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Groner J. P., Watson A. J., Bach F. H. Dw/LD-related molecular polymorphism of DR4 beta-chains. J Exp Med. 1983 May 1;157(5):1687–1691. doi: 10.1084/jem.157.5.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gustafsson K., Wiman K., Emmoth E., Larhammar D., Böhme J., Hyldig-Nielsen J. J., Ronne H., Peterson P. A., Rask L. Mutations and selection in the generation of class II histocompatibility antigen polymorphism. EMBO J. 1984 Jul;3(7):1655–1661. doi: 10.1002/j.1460-2075.1984.tb02026.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hurley C. K., Giles R. C., Nunez G., DeMars R., Nadler L., Winchester R., Stastny P., Capra J. D. Molecular localization of human class II MT2 and MT3 determinants. J Exp Med. 1984 Aug 1;160(2):472–493. doi: 10.1084/jem.160.2.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Larhammar D., Andersson G., Andersson M., Bill P., Böhme J., Claesson L., Denaro M., Emmoth E., Gustafsson K., Hammarling U. Molecular analysis of human class II transplantation antigens and their genes. Hum Immunol. 1983 Sep;8(1):95–103. doi: 10.1016/0198-8859(83)90087-3. [DOI] [PubMed] [Google Scholar]
  13. Larhammar D., Servenius B., Rask L., Peterson P. A. Characterization of an HLA DR beta pseudogene. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1475–1479. doi: 10.1073/pnas.82.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Long E. O., Wake C. T., Gorski J., Mach B. Complete sequence of an HLA-dR beta chain deduced from a cDNA clone and identification of multiple non-allelic DR beta chain genes. EMBO J. 1983;2(3):389–394. doi: 10.1002/j.1460-2075.1983.tb01435.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McIntyre K. R., Seidman J. G. Nucleotide sequence of mutant I-A beta bm12 gene is evidence for genetic exchange between mouse immune response genes. Nature. 1984 Apr 5;308(5959):551–553. doi: 10.1038/308551a0. [DOI] [PubMed] [Google Scholar]
  16. Mukai R., Suzuki M., Yabe T., Hamaguchi H., Maeda H. Identification of the MT3 molecule from HLA-DR4, 7, and w9 homozygous cell lines. J Immunol. 1984 Dec;133(6):3211–3219. [PubMed] [Google Scholar]
  17. Nepom B. S., Nepom G. T., Mickelson E., Antonelli P., Hansen J. A. Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between beta-chain diversity and HLA-D. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6962–6966. doi: 10.1073/pnas.80.22.6962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nicklas J. A., Noreen H. J., Segall M., Bach F. H. Southern analysis of DNA polymorphism among Dw subtypes of DR4. Hum Immunol. 1985 Jun;13(2):95–103. doi: 10.1016/0198-8859(85)90016-3. [DOI] [PubMed] [Google Scholar]
  19. Rask L., Gustafsson K., Larhammar D., Ronne H., Peterson P. A. Generation of class II antigen polymorphism. Immunol Rev. 1985 Jul;84:123–143. doi: 10.1111/j.1600-065x.1985.tb01128.x. [DOI] [PubMed] [Google Scholar]
  20. Reinsmoen N. L., Bach F. H. Five HLA-D clusters associated with HLA-DR4. Hum Immunol. 1982 Jun;4(3):249–258. doi: 10.1016/0198-8859(82)90040-4. [DOI] [PubMed] [Google Scholar]
  21. Ronne H., Widmark E., Rask L., Peterson P. A. Intron sequences reveal evolutionary relationships among major histocompatibility complex class I genes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5860–5864. doi: 10.1073/pnas.82.17.5860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Segall M., Cairns J. S., Dahl C. A., Curtsinger J. M., Freeman S., Nelson P. J., Cohen O., Wu S., Nicklas J. N., Noreen H. J. DNA and protein studies of HLA class II molecules: their relationship to T cell recognition. Immunol Rev. 1985 Jul;85:129–148. doi: 10.1111/j.1600-065x.1985.tb01133.x. [DOI] [PubMed] [Google Scholar]
  24. Shackelford D. A., Kaufman J. F., Korman A. J., Strominger J. L. HLA-DR antigens: structure, separation of subpopulations, gene cloning and function. Immunol Rev. 1982;66:133–187. doi: 10.1111/j.1600-065x.1982.tb00437.x. [DOI] [PubMed] [Google Scholar]
  25. Spies T., Sorrentino R., Boss J. M., Okada K., Strominger J. L. Structural organization of the DR subregion of the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5165–5169. doi: 10.1073/pnas.82.15.5165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Suzuki M., Yabe T., Satake M., Juji T., Hamaguchi H. Two-dimensional gel electrophoretic analysis of the MT3 and DR4 molecules from the different D-typed cells. J Exp Med. 1984 Sep 1;160(3):751–758. doi: 10.1084/jem.160.3.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tykocinski M. L., Max E. E. CG dinucleotide clusters in MHC genes and in 5' demethylated genes. Nucleic Acids Res. 1984 May 25;12(10):4385–4396. doi: 10.1093/nar/12.10.4385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Widera G., Flavell R. A. The nucleotide sequence of the murine I-E beta b immune response gene: evidence for gene conversion events in class II genes of the major histocompatibility complex. EMBO J. 1984 Jun;3(6):1221–1225. doi: 10.1002/j.1460-2075.1984.tb01956.x. [DOI] [PMC free article] [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