The Class I HLA Repertoire of Pancreatic Islets Comprises the Nonclassical Class Ib Antigen HLA-G

  1. Vincenzo Cirulli1,
  2. Jessie Zalatan2,
  3. Michael McMaster3,
  4. Robyn Prinsen2,
  5. Daniel R. Salomon2,
  6. Camillo Ricordi4,
  7. Bruce E. Torbett2,
  8. Paolo Meda5 and
  9. Laura Crisa2
  1. 1Whittier Institute for Diabetes, University of California San Diego, La Jolla, California
  2. 2Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California
  3. 3Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, California
  4. 4Diabetes Research Institute, University of Miami School of Medicine, Miami, Florida
  5. 5Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
  1. Address correspondence and reprint requests to Laura Crisa, MD, PhD, Department of Molecular and Experimental Medicine, MEM55, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. E-mail: crisa{at}scripps.edu

Abstract

Selective expression of the human class Ib HLA molecule HLA-G in immunologically protected sites and its function in the inhibition of NK and T-cell effector functions support an important role of this molecule in immunoregulation. Here, we demonstrate that HLA-G is constitutively expressed in the endocrine compartment of the human pancreas. Surface expression of this HLA determinant in endocrine cells is regulated in response to growth and inflammatory stimuli. Furthermore, we provide evidence that HLA-G expressed in this tissue may associate with a subset of insulin-containing granules and may be shuttled to the cell surface in response to secretory stimuli. Thus, HLA-G presentation by endocrine cells may be regulated in concert with their secretory activity. These results identify the expression of a major histocompatibility complex locus with putative regulatory functions in human pancreatic islets, a finding with potentially important implications for the progression of autoimmunity as well as for the establishment of transplant tolerance to this tissue.

Footnotes

  • Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted February 16, 2006.
    • Received July 7, 2005.
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