Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1994 Jan;53(1):58–60. doi: 10.1136/ard.53.1.58

Analysis of the MHC class II encoded components of the HLA class I antigen processing pathway in ankylosing spondylitis.

R O Burney 1, K D Pile 1, K Gibson 1, A Calin 1, L G Kennedy 1, P J Sinnott 1, S H Powis 1, B P Wordsworth 1
PMCID: PMC1005245  PMID: 8311558

Abstract

OBJECTIVES--The evaluation of the role of polymorphism within the class II encoded antigen processing genes, LMP2 and TAP, in susceptibility to ankylosing spondylitis (AS). METHODS--Eighty five patients with ankylosing spondylitis, 35 B27 positive healthy controls, and 55 unrelated healthy controls were studied. TAP1 and TAP2 alleles were assigned by ARMS PCR, and LMP2 alleles were assigned by restriction enzyme digestion of a PCR product. RESULTS--The TAP1C allele was increased in the AS group (6%) compared with random controls (1%), p = 0.03 and TAP2E was increased in AS (3.5%) compared with random controls (0%), p = 0.05. However, the frequencies of these alleles were also increased in B27 matched controls. There were no differences in LMP2 allele or genotype frequencies between AS and either of the control groups. Partitioning of patients according to presence or absence of uveitis did not reveal any significant associations. CONCLUSIONS--Increases of the minor TAP alleles, 1C and 2E, in AS reflect linkage disequilibrium between these alleles and HLA-B27. Polymorphism of the class I antigen processing pathway does not contribute significantly to AS susceptibility nor to the development of anterior uveitis associated with AS.

Full text

PDF
58

Images in this article

59Image
on p.59

Selected References

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

  1. Beck S., Kelly A., Radley E., Khurshid F., Alderton R. P., Trowsdale J. DNA sequence analysis of 66 kb of the human MHC class II region encoding a cluster of genes for antigen processing. J Mol Biol. 1992 Nov 20;228(2):433–441. doi: 10.1016/0022-2836(92)90832-5. [DOI] [PubMed] [Google Scholar]
  2. Benjamin R., Parham P. HLA-B27 and disease: a consequence of inadvertent antigen presentation? Rheum Dis Clin North Am. 1992 Feb;18(1):11–21. [PubMed] [Google Scholar]
  3. Edmunds L., Elswood J., Calin A. New light on uveitis in ankylosing spondylitis. J Rheumatol. 1991 Jan;18(1):50–52. [PubMed] [Google Scholar]
  4. Elliott T. How do peptides associate with MHC class I molecules? Immunol Today. 1991 Nov;12(11):386–388. doi: 10.1016/0167-5699(91)90134-f. [DOI] [PubMed] [Google Scholar]
  5. Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. Identification of self peptides bound to purified HLA-B27. Nature. 1991 Sep 26;353(6342):326–329. doi: 10.1038/353326a0. [DOI] [PubMed] [Google Scholar]
  6. Madden D. R., Gorga J. C., Strominger J. L., Wiley D. C. The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell. 1992 Sep 18;70(6):1035–1048. doi: 10.1016/0092-8674(92)90252-8. [DOI] [PubMed] [Google Scholar]
  7. Monaco J. J. A molecular model of MHC class-I-restricted antigen processing. Immunol Today. 1992 May;13(5):173–179. doi: 10.1016/0167-5699(92)90122-N. [DOI] [PubMed] [Google Scholar]
  8. Monaco J. J., McDevitt H. O. Identification of a fourth class of proteins linked to the murine major histocompatibility complex. Proc Natl Acad Sci U S A. 1982 May;79(9):3001–3005. doi: 10.1073/pnas.79.9.3001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Pazmany L., Rowland-Jones S., Huet S., Hill A., Sutton J., Murray R., Brooks J., McMichael A. Genetic modulation of antigen presentation by HLA-B27 molecules. J Exp Med. 1992 Feb 1;175(2):361–369. doi: 10.1084/jem.175.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Powis S. H., Tonks S., Mockridge I., Kelly A. P., Bodmer J. G., Trowsdale J. Alleles and haplotypes of the MHC-encoded ABC transporters TAP1 and TAP2. Immunogenetics. 1993;37(5):373–380. doi: 10.1007/BF00216802. [DOI] [PubMed] [Google Scholar]
  11. Powis S. J., Deverson E. V., Coadwell W. J., Ciruela A., Huskisson N. S., Smith H., Butcher G. W., Howard J. C. Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule. Nature. 1992 May 21;357(6375):211–215. doi: 10.1038/357211a0. [DOI] [PubMed] [Google Scholar]
  12. Robinson W. P., van der Linden S. M., Khan M. A., Rentsch H. U., Cats A., Russell A., Thomson G. HLA-Bw60 increases susceptibility to ankylosing spondylitis in HLA-B27+ patients. Arthritis Rheum. 1989 Sep;32(9):1135–1141. doi: 10.1002/anr.1780320912. [DOI] [PubMed] [Google Scholar]
  13. Townsend A., Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. doi: 10.1146/annurev.iy.07.040189.003125. [DOI] [PubMed] [Google Scholar]
  14. Wordsworth B. P., Pile K. D., Gibson K., Burney R. O., Mockridge I., Powis S. H. Analysis of the MHC-encoded transporters TAP1 and TAP2 in rheumatoid arthritis: linkage with DR4 accounts for the association with a minor TAP2 allele. Tissue Antigens. 1993 Sep;42(3):153–155. doi: 10.1111/j.1399-0039.1993.tb02185.x. [DOI] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES