Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Feb 1;159(2):394–404. doi: 10.1084/jem.159.2.394

The HLA-DR4 family of haplotypes consists of series of distinct DR and DS molecules

PMCID: PMC2187232  PMID: 6420500

Abstract

Among DR4-associated HLA-D antigens, distinct and consistent structural variations were found for the products of two human "Ia-like" loci, DR and DS. Analysis of neuraminidase-treated immunoprecipitated DR molecules from 15 HLA-DR4-associated HLA-D homozygous B-lymphoblastoid cell lines by two dimensional polyacrylamide gel electrophoresis identified five distinct DR beta chains. In addition, gel analysis of immunoprecipitated DS molecules identified three distinct DS beta chains. Altogether, five distinct DR4 haplotypes were defined according to the observed structural diversity of the DR and DS beta chains. These gene products presumably contribute the dominant polymorphisms recognized by T cells in mixed lymphocyte reaction (MLR). Thus, these studies indicate that the serologic specificity known as HLA-DR4 is not a single haplotype, but a determinant present on products of individual loci arrayed into distinctly different haplotypes. These findings suggest that distinct products of individual loci, rather than conventional HLA specificities defined by alloimmune sera, may represent the genetic markers relevant to HLA-D/DR associated diseases.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Allison J. P., Walker L. E., Russell W. A., Pellegrino M. A., Ferrone S., Reisfeld R. A., Frelinger J. A., Silver J. Murine Ia and human DR antigens: homology of amino-terminal sequences. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3953–3956. doi: 10.1073/pnas.75.8.3953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benacerraf B. Role of MHC gene products in immune regulation. Science. 1981 Jun 12;212(4500):1229–1238. doi: 10.1126/science.6165083. [DOI] [PubMed] [Google Scholar]
  3. Bias W. B., Hsu S. H., Pollard M. K., Harvey J., Lotze M. T., Arnett F. C., Stevens M. B. HLA-DR characterization of a Chippewa Indian subpopulation with high prevalence of rheumatoid arthritis. Hum Immunol. 1981 Mar;2(2):155–163. doi: 10.1016/0198-8859(81)90062-8. [DOI] [PubMed] [Google Scholar]
  4. Corte G., Calabi F., Damiani G., Bargellesi A., Tosi R., Sorrentino R. Human Ia molecules carrying DC1 determinants differ in both alpha- and beta-subunits from Ia molecules carrying DR determinants. Nature. 1981 Jul 23;292(5821):357–360. doi: 10.1038/292357a0. [DOI] [PubMed] [Google Scholar]
  5. Fuller T. C., Einarson M., Pinto C., Ahern A., Yunis E. J. Genetic evidence that HLA-DR (Ia) specificities include multiple HLA-D determinants on a single haplotype. Transplant Proc. 1978 Dec;10(4):781–784. [PubMed] [Google Scholar]
  6. Goyert S. M., Gatti R., Silver J. Peptide map comparisons of similar serologically defined HLA-DR antigens isolated from different lymphoblastoid cell lines. Hum Immunol. 1982 Nov;5(3):205–214. doi: 10.1016/0198-8859(82)90133-1. [DOI] [PubMed] [Google Scholar]
  7. Goyert S. M., Shively J. E., Silver J. Biochemical characterization of a second family of human Ia molecules, HLA-DS, equivalent to murine I-A subregion molecules. J Exp Med. 1982 Aug 1;156(2):550–566. doi: 10.1084/jem.156.2.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Grosse-Wilde H., Hauptmann G., Johannsen R., Netzel B., Rittner C., Ruppelt W. Population data on two new HLA-D determinants, EI and RE. Scand J Immunol. 1977;6(5):515–521. doi: 10.1111/j.1365-3083.1977.tb02114.x. [DOI] [PubMed] [Google Scholar]
  10. Hanrahan L. R., Jr, Mehta C., Reinsmoen N. L., Yunis E. J. Linkage disequilibrium between HLA-B13 and HLA-D. Transplant Proc. 1977 Dec;9(4):1729–1732. [PubMed] [Google Scholar]
  11. Hsu S. H., Lambert P., Scribner P. P., Hartzman R. J., Robbins F., Bias W. B. Primary and secondary MLR characterization of three allelic variants of HLA-Dw7 segregating in a single family. Hum Immunol. 1983 Mar;6(3):167–176. doi: 10.1016/0198-8859(83)90099-x. [DOI] [PubMed] [Google Scholar]
  12. Klein J., Figueroa F. Polymorphism of the mouse H-2 loci. Immunol Rev. 1981;60:23–57. doi: 10.1111/j.1600-065x.1981.tb00361.x. [DOI] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. McDevitt H. O. Regulation of the immune response by the major histocompatibility system. N Engl J Med. 1980 Dec 25;303(26):1514–1517. doi: 10.1056/NEJM198012253032606. [DOI] [PubMed] [Google Scholar]
  15. McDevitt H. O. The role of H-2 I region genes in regulation of the immune response. J Immunogenet. 1981 Aug;8(4):287–295. doi: 10.1111/j.1744-313x.1981.tb00771.x. [DOI] [PubMed] [Google Scholar]
  16. Mickelson E. M., Nisperos B., Hansen J. A. Two homozygous typing cells defining a subgroup of HLA-Dw6. Hum Immunol. 1980 Dec;1(4):363–368. doi: 10.1016/0198-8859(80)90112-3. [DOI] [PubMed] [Google Scholar]
  17. Mickelson E. M., Nisperos B., Layrisse Z., Kim S. J., Thomas E. D., Hansen J. A. Analysis of the HLA-DRw8 haplotype: recognition by HTC typing of three distinct antigen complexes in Caucasians, Native Americans, and Orientals. Immunogenetics. 1983;17(4):399–410. doi: 10.1007/BF00372458. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Niederhuber J. E., Frelinger J. A. Expression of Ia antigens on T and B cells and their relationship to immune-response functions. Transplant Rev. 1976;30:101–121. [PubMed] [Google Scholar]
  20. Nose Y., Sato K., Nakagawa M., Kondoh K., Inouye H., Tsuji K. HLA-D clusters associated with DR4 in the Japanese population. Hum Immunol. 1982 Nov;5(3):199–203. doi: 10.1016/0198-8859(82)90132-x. [DOI] [PubMed] [Google Scholar]
  21. O'Farrell P. Z., Goodman H. M., O'Farrell P. H. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. doi: 10.1016/0092-8674(77)90176-3. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Reinsmoen N. L., Sasazuki T., Kaneoka H., Ohta N., Noreen H. J., Greenberg L. J., Kersey J. H. Two distinct HLA-D specificities (DHO and Dw2) in linkage with HLA-DRw2 as defined in white and Japanese populations. Transplant Proc. 1978 Dec;10(4):789–791. [PubMed] [Google Scholar]
  24. Rosenthal A. S. Determinant selection and macrophage function in genetic control of the immune response. Immunol Rev. 1978;40:136–152. doi: 10.1111/j.1600-065x.1978.tb00404.x. [DOI] [PubMed] [Google Scholar]
  25. Sasazuki T., McMichael A., Payne R., McDevitt H. O. HLA-D antigens in the Japanese population. Tissue Antigens. 1977 May;9(5):267–272. doi: 10.1111/j.1399-0039.1977.tb01117.x. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Shackelford D. A., Strominger J. L. Analysis of the oligosaccharides on the HLA-DR and DC1 B cell antigens. J Immunol. 1983 Jan;130(1):274–282. [PubMed] [Google Scholar]
  28. Suciu-Foca N., Godfrey M., Khan G., Woodward K., Rohowsky C., Reed E., Hardy M., Reemtsma K. New HLA-D alleles associated with DR1 and DR2. Tissue Antigens. 1981 Mar;17(3):294–302. doi: 10.1111/j.1399-0039.1981.tb00704.x. [DOI] [PubMed] [Google Scholar]
  29. Yunis E. J., Amos D. B. Three closely linked genetic systems relevant to transplantation. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3031–3035. doi: 10.1073/pnas.68.12.3031. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES