Widespread expression of the nonclassical class I Qa-2 antigens in hemopoietic and nonhemopoietic cells.

We reexamined expression patterns of one of the best characterized mouse class Ib MHC molecules, Qa-2. Transcripts encoding glycosylphosphatidylinositol-linked and soluble forms of Qa-2 are expressed in all organs except brain. The membrane-bound Qa-2 proteins are detectable, to varying degrees, in many cell types of immunological interest: on professional antigen-presenting cells capable of inducing anti-Qa-2 allogeneic responses, on thymic epithelial cells essential for T-cell positive selection, on mature as well as immature thymocytes, in immunologically privileged sites (testis/spermatazoa), and on cells implicated in mucosal immunity (lymphoid-derived and epithelial gut cells and hepatocytes). Although Qa-2 has a nearly ubiquitous tissue distribution similar to H2-Kb and Db molecules, the relative levels of Qa-2 and class Ia displayed on cell surfaces vary in a cell-specific fashion. Analyses of primary cell lines derived from normal mouse tissues also support the conclusion that Qa-2 is present in all cells that can express class Ia antigens. In contrast, tumor lines from Qa-2-positive mice are frequently Qa-2 deficient, suggesting that the Qa-2-negative phenotype of malignant cells is selected in vivo.

Expression of a nonclassical MHC class Ib molecule in the eye.

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.

Interaction of 2C T cells with a hybrid Ld molecule bearing an alpha 3 domain derived from the class IB molecule, Qa-2.

The CD8 co-receptor interacts with nonpolymorphic residues on class I molecules. LQ3, a laboratory engineered Ld molecule bearing an alpha 3 domain derived from Q7 (Qa-2), interacts poorly with anti-Ld CD8-dependent T cells. 2C TCR transgenic mice bear a receptor specific for the p2Ca peptide bound to Ld. The authors show that although this peptide interacts with LQ3, LQ3 APC fail to activate splenic 2C CD8 T cells in vitro in the absence of IL-2, while control Ld APC do. The authors have used this receptor ligand pair to examine negative selection within the thymus of (B6 x C3H.Ld)F1 versus (B6 x C3H.LQ3)F1 radiation chimeras repopulated with 2C bone marrow cells. While positive selection occurs normally in (B6 x C3H)F1 chimeras, animals expressing either Ld or LQ3 fail to generate 2C CD8+ cells. Thus, either CD8 is not required for negative selection of this TCR or a weak interaction of CD8 with LQ3 is sufficient. TSA-1, a developmentally regulated marker, was used to follow the process of negative selection. The results show that deletion of 2C T cells does not occur until thymocytes reach the double positive (DP) stage. Furthermore, the authors noted a small population of DP TSA-1hi cells remains, while DP TSA-1int and TSA-1lo cells are absent. These data support the notion that thymocytes either reach a particular stage of development or locate in an appropriate intrathymic compartment before they undergo negative selection.

Relationships of serum opsonins and complement in human experimental gingivitis.

This study assessed the phagocytosis of polymorphonuclear neutrophils and the opsonic capacity of serum in experimental human gingivitis. Relationships were sought among these two measurements, clinical indices of gingivitis and complement-related opsonins. Measurements of chemiluminescence provided an index of phagocytosis and of opsonic capacity. Test group Plaque Index scores were higher than the control group on Days 7, 14, and 21, while the Gingival Index of the test group was elevated only on Day 21. Phagocytosis of test subjects' PMNs and opsonic capacity of their sera were no different from that of the controls'. Levels of C3 in both nonactivated and activated sera of the test group were significantly lower than that of the control group only on Day 14. In the test group, differences of per cent C3 conversion occurred between Days 14 and 21, and Plaque Index scores were inversely correlated with the order of per cent C3 data on these same days. Our results also indicate that complement contributes significantly to the serum opsonic capacity. The levels of developing plaque and subsequent gingival inflammation are apparently related to the degree of complement activation.