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. 1982 Feb;69(2):443–450. doi: 10.1172/JCI110468

Structural Identity of Human Histocompatibility Leukocyte Antigen-B27 Molecules from Patients with Ankylosing Spondylitis and Normal Individuals

Robert W Karr 1, Yaffa Hahn 1, Benjamin D Schwartz 1
PMCID: PMC370994  PMID: 7056855

Abstract

Although the association between human histocompatibility leukocyte antigen (HLA) B27 and ankylosing spondylitis is the prototype of HLA-disease association, the mechanism underlying these associations has not been determined. We have investigated the possibility that the B27 molecules from patients with ankylosing spondylitis are different from those of normals, and only the “different” molecules predispose the individual to disease. Biosynthetically radiolabeled HLA-B27 molecules from patients with ankylosing spondylitis and normal individuals were compared by two-dimensional gel electrophoresis and tryptic peptide mapping with high pressure liquid chromatography. Extensive charge heterogeneity in the 45,000-dalton heavy chain was detected when B27 molecules were analyzed by two-dimensional gel electrophoresis; the charge heterogeneity was reduced, but not eliminated, when the B27 molecules were treated with neuraminidase to remove sialic acid residues before analysis. No structural difference in the B27 molecules from an ankylosing spondylitis patient and a normal individual were detected by two-dimensional gel electrophoresis. Analysis of [3H]leucine-labeled and [3H]arginine-labeled tryptic peptides and chymotryptic peptides of the trypsin insoluble material by reverse-phase high pressure liquid chromatography revealed identity of the B27 molecules from ankylosing spondylitis patients and normal individuals. These studies indicate that development of akylosing spondylitis in only some B27 positive individuals is not attributable to those individuals possessing variant B27 molecules.

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Selected References

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

  1. Biddison W. E., Krangel M. S., Strominger J. L., Ward F. E., Shearer G. M., Shaw S. Virus-immune cytotoxic T cells recognize structural differences between serologically indistinguishable HLA-A2 molecules. Hum Immunol. 1980 Oct;1(3):225–232. doi: 10.1016/0198-8859(80)90017-8. [DOI] [PubMed] [Google Scholar]
  2. Brewerton D. A., Hart F. D., Nicholls A., Caffrey M., James D. C., Sturrock R. D. Ankylosing spondylitis and HL-A 27. Lancet. 1973 Apr 28;1(7809):904–907. doi: 10.1016/s0140-6736(73)91360-3. [DOI] [PubMed] [Google Scholar]
  3. Brown J. L., Nathenson S. G. Structural differences between parent and mutant H-2K glycoproteins from two H-2K gene mutants: b6.c-h-2ba (Hzl) and B6-H-2bd (M505). J Immunol. 1977 Jan;118(1):98–102. [PubMed] [Google Scholar]
  4. Calin A., Fries J. F. Striking prevalence of ankylosing spondylitis in "healthy" w27 positive males and females. N Engl J Med. 1975 Oct 23;293(17):835–839. doi: 10.1056/NEJM197510232931701. [DOI] [PubMed] [Google Scholar]
  5. Cohen L. M., Mittal K. K., Schmid F. R., Rogers L. F., Cohen K. L. Increased risk for spondylitis stigmata in apparently healthy HL-AW27 men. Ann Intern Med. 1976 Jan;84(1):1–7. doi: 10.7326/0003-4819-84-1-1. [DOI] [PubMed] [Google Scholar]
  6. Grumet F. C., Fendly B. M., Engleman E. G. Monoclonal anti-HLA-B27 antibody (B27M1): production and lack of detectable typing difference between patients with ankylosing spondylitis, Reiter's syndrome, and normal controls. Lancet. 1981 Jul 25;2(8239):174–176. doi: 10.1016/s0140-6736(81)90358-5. [DOI] [PubMed] [Google Scholar]
  7. Hancock W. S., Bishop C. A., Prestidge R. L., Hearn M. T. The use of high pressure liquid chromatography (hplc) for peptide mapping of proteins. IV. Anal Biochem. 1978 Aug 15;89(1):203–212. doi: 10.1016/0003-2697(78)90742-x. [DOI] [PubMed] [Google Scholar]
  8. Jones P. P. Analysis of H-2 and Ia molecules by two-dimensional gel electrophoresis. J Exp Med. 1977 Nov 1;146(5):1261–1279. doi: 10.1084/jem.146.5.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Khan M. A., Braun W. E., Kushner I., Grecek D. E., Muir W. A., Steinberg A. G. HLA B27 in ankylosing spondylitis: differences in frequency and relative risk in American Blacks and Caucasians. J Rheumatol Suppl. 1977;3:39–43. [PubMed] [Google Scholar]
  10. Krakauer T., Hansen T. H., Camerini-Otero R. D., Sachs D. H. Analysis of the heterogeneity of the mouse H-2K, D, and L gene products. J Immunol. 1980 May;124(5):2149–2156. [PubMed] [Google Scholar]
  11. 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]
  12. McMichael A. J., Parham P., Rust N., Brodsky F. A monoclonal antibody that recognizes an antigenic determinant shared by HLA A2 and B17. Hum Immunol. 1980 Sep;1(2):121–129. doi: 10.1016/0198-8859(80)90099-3. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Nisizawa T., Ewenstein B. M., Uehara H., McGovern D., Nathenson S. G. Biochemical studies on the H-2K antigens of the MHC mutant bml. Immunogenetics. 1981;12(1-2):33–44. doi: 10.1007/BF01561649. [DOI] [PubMed] [Google Scholar]
  15. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  16. Orr H. T., Lopez de Castro J. A., Parham P., Ploegh H. L., Strominger J. L. Comparison of amino acid sequences of two human histocompatibility antigens, HLA-A2 and HLA-B7: location of putative alloantigenic sites. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4395–4399. doi: 10.1073/pnas.76.9.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Parham P., Barnstable C. J., Bodmer W. F. Use of a monoclonal antibody (W6/32) in structural studies of HLA-A,B,C, antigens. J Immunol. 1979 Jul;123(1):342–349. [PubMed] [Google Scholar]
  18. Parham P., Bodmer W. F. Monoclonal antibody to a human histocompatibility alloantigen, HLA-A2. Nature. 1978 Nov 23;276(5686):397–399. doi: 10.1038/276397a0. [DOI] [PubMed] [Google Scholar]
  19. Parham P., Humphreys R. E., Turner M. J., Strominger J. L. Heterogeneity of HL-A antigen preparations is due to variable sialic acid content. Proc Natl Acad Sci U S A. 1974 Oct;71(10):3998–4001. doi: 10.1073/pnas.71.10.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ploegh H. L., Orr H. T., Strominger J. L. Major histocompatibility antigens: the human (HLA-A, -B, -C) and murine (H-2K, H-2D) class I molecules. Cell. 1981 May;24(2):287–299. doi: 10.1016/0092-8674(81)90318-4. [DOI] [PubMed] [Google Scholar]
  21. Schlosstein L., Terasaki P. I., Bluestone R., Pearson C. M. High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med. 1973 Apr 5;288(14):704–706. doi: 10.1056/NEJM197304052881403. [DOI] [PubMed] [Google Scholar]
  22. Schwartz B. D., Luehrman L. K., Rodey G. E. Public antigenic determinant on a family of HLA-B molecules. J Clin Invest. 1979 Oct;64(4):938–947. doi: 10.1172/JCI109560. [DOI] [PMC free article] [PubMed] [Google Scholar]

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