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Rheumatology Advance Access originally published online on February 19, 2007
Rheumatology 2007 46(5):893-894; doi:10.1093/rheumatology/kel441
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Response to Gauster et al.

R. L. Allen

Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK

Correspondence to: E-mail: rla25{at}cam.ac.uk

SIR, We would like to thank Dr Gauster and his colleagues for their interest in our article and their helpful comments regarding the figure on trophoblast MHC-I. In our article, we aimed to assess the relative levels of MHC-I heavy chains compared with conformed MHC-I on the surface of cells from healthy controls and arthritis patients using the monoclonal antibodies HC10 and W6/32. MHC-I heavy chains, as indicated by HC10 reactivity, have been been implicated in the pathogenesis of spondyloarthropathy [1, 2], and we observed an increase in the relative levels of MHC-I heavy chains for arthritic patients compared with healthy controls.

In Figure 4 of our manuscript we used the same antibodies to examine MHC-I heavy chains on trophoblast, as it has been suggested that recognition of FHC on this tissue could contribute to maternal immunoregulation during pregnancy [3]. We again used HC10, in order to allow comparison with results from peripheral blood, and because this antibody had previously been shown to immunoprecipitate both HLA-C and HLA-G [4]. The findings of Gauster and colleagues show that the reactivity of HC10 with HLA-G is not sufficient to stain cells by immunohistochemistry. If a similar situation exists for flow cytometry, it indicates that the particularly high levels of MHC-I heavy chains we observed on trophoblast are, in fact, an underestimate. Thus, in addition to the HLA-G structures previously described [5–7], we can now conclude that trophoblast HLA-C appears to be present at unusually high levels as heavy chains. If trophoblast MHC-I heavy chain levels are, as Dr Gauster's findings suggest, even higher than our original estimate, it will be important to address their functional relevance. MHC-I heavy chains have been shown to act as a ligand for inhibitory LILR receptors, which are found on maternal decidual macrophages [8, 9], and may therefore suppress maternal macrophage activity. We believe that recognition of MHC-I heavy chains by LILR will prove to be an exciting field in the immunology of pregnancy.

The author has declared no conflicts of interest.


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 References
 

  1. Khare SD, Hansen J, Luthra HS, David CS. (1996) HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/Human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m. J Clin Invest 98:2746–55.[Web of Science][Medline]
  2. Khare SD, Bull MJ, Hanson J, Luthra HS, David CS. (1998) Spontaneous inflammatory disease in HLA-B27 transgenic mice is independent of MHC class II molecules: a direct role for B27 heavy chains and not B27-derived peptides. J Immunol 160:101–6.[Abstract/Free Full Text]
  3. Raine T and Allen RL. (2005) MHC-I recognition by receptors on myelomonocytic cells: new tricks for old dogs? BioEssays 27:542–50.[CrossRef][Web of Science][Medline]
  4. Sernee MF, Ploegh HL, Schust DJ. (1998) Why certain antibodies cross-react with HLA-A and HLA-G: epitope mapping of two common MHC class I reagents. Mol Immunol 35:177–88.[CrossRef][Web of Science][Medline]
  5. Gonen-Gross T, Gazit R, Achdout H, et al. (2003) Special organization of the HLA-G protein on the cell surface. Hum Immunol 64:1011–6.[CrossRef][Web of Science][Medline]
  6. Gonen-Gross T, Achdout H, Gazit R, et al. (2003) Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. J Immunol 171:1343–51.[Abstract/Free Full Text]
  7. Boyson JE, Erskine R, Whitman MC, et al. (2002) Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci USA 99:16180–5.[Abstract/Free Full Text]
  8. Allen RL, Raine T, Haude A, Trowsdale J, Wilson MJ. (2001) Leukocyte receptor complex-encoded immunomodulatory receptors show differing specificity for alternative HLA-B27 structures. J Immunol 167:5543–7.[Abstract/Free Full Text]
  9. Petroff MG, Sedlmayr P, Azzola D, Hunt JS. (2002) Decidual macrophages are potentially susceptible to inhibition by class Ia and class Ib HLA molecules. J Reprod Immunol 56:3–17.[CrossRef][Web of Science][Medline]
Accepted 8 December 2006


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This Article
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