EXPRESSION OF A NONCLASSICAL MHC CLASS Ib MOLECULE IN THE EYE1

BACKGROUND MHC class Ia molecules are absent, or expressed at low levels, on cells lining the anterior chamber of the eye, an immune-privileged site. Although the scarcity of class Ia MHC antigens may protect cells from T cell-mediated tissue injury, it may also render them vulnerable to natural killer cell-mediated cytolysis. There is growing evidence that MHC class Ib molecules share similar functions to class Ia. In this study, we examine the expression and distribution of Qa-2, one of the best-characterized murine MHC class Ib molecules in the eye. METHODS The transcription of Qa-2 mRNA in whole eye and eye-derived cells was analyzed by sensitive and specific RNase protection and reverse transcription-polymerase chain reaction assays. Immunohistochemistry, flow cytometry, and ELISA were used to determine whether Qa-2 was expressed as cell surface proteins. Expression levels of Qa-2 were monitored in resting cells and cells stimulated with interferon-gamma. RESULTS Expression of membrane-bound and soluble Qa-2 isoforms was detected in various tissues of the eye, including cell subsets lining the anterior chamber. Immunohistological staining revealed Qa-2 expression on corneal epithelium as well as endothelium, iris ciliary bodies, and retina. These observations were confirmed by analysis of cultured, eye-derived cells. Qa-2 expression was inducible by interferon-gamma. Qa-2 was not detected in lens cells. CONCLUSIONS The results demonstrate that membrane-bound and soluble MHC class Ib molecules are expressed by eye cells. Expression of Qa-2 in the corneal endothelium and other substructures lining the anterior chamber suggests that this class Ib protein may contribute to the immune-privileged status of the anterior chamber.