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

¹ Whittier Institute for Diabetes, University of California San Diego, La Jolla, California
² Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California
³ Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, California
⁴ Diabetes Research Institute, University of Miami School of Medicine, Miami, Florida
⁵ Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland

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

Abbreviations: IFN-, -interferon; IL, interleukin; INF-, -interferon; MHC, major histocompatibility complex; PECAM, platelet-endothelial cell adhesion molecule

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.

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