Expression of Inhibitory Receptors Ly49E and CD94/NKG2 on Fetal Thymic and Adult Epidermal TCR Vγ3 Lymphocytes

Abstract

Ly49 and CD94/NKG2 inhibitory receptors are predominantly expressed on murine NK cells, but they are also expressed on a subpopulation of peripheral CD8 memory TCR αβ lymphocytes. In this study we demonstrate that Ly49E and CD94/NKG2 receptors are expressed on mature TCR Vγ3+ cells in the fetal thymus. Expression correlated with a memory phenotype, such as expression of CD44, 2B4, and IL-2Rβ (CD122), and absence of IL-2Rα (CD25) expression. No expression of Ly49A, C, D, G2, or I receptors was observed. This phenotype is similar to that of fetal thymic NK cells. Skin-located Vγ3 T cells, the progeny of fetal thymic Vγ3 cells, also expressed CD94/NKG2 and Ly49E but not the other members of the Ly49 family. The development and survival of Ly49E+ or CD94/NKG2+ Vγ3 T lymphocytes was not dependent upon expression of MHC class I molecules. The cytotoxicity of TCR Vγ3 cells was inhibited when Qdm, the ligand for CD94/NKG2, was presented by Qa1b-transfected target cells. Also, upon cross-linking of CD94/NKG2 with mAb 3S9, TCR Vγ3 thymocytes were prevented from killing FcγR+ P815 target cells. These effects were most pronounced in the CD94/NKG2high subpopulation as compared with the CD94/NKG2low subpopulation of Vγ3 cells. Our data demonstrate that Vγ3 T cells expressing inhibitory Ly49E and CD94/NKG2 receptors are mature and display a memory phenotype, and that CD94/NKG2 functions as an inhibitory receptor on these T lymphocytes.

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

“…Thus, the available data suggest that the majority of Ly49 receptors expressed in B6 mice are specific for classical MHC-I molecules. No MHC-I ligand has been identified for the activating Ly49H, which binds to the MCMV m157 protein (27,28), and no ligand is known for Ly49E, which is predominantly expressed in fetal NK cells and certain TCR␥␦ T cells (17,29).…”

DifferentialLy49eExpression Pathways in Resting versus TCR-Activated Intraepithelial γδ T Cells

“…In B6 mice, only 20% of resting DETCs express Ly49E (11). Because Ly49E expression is selectively induced on a considerable proportion of NK cells upon IL-2 culture (19) and because DETCs acquire CD122 (IL-2Rb) during their intrathymic maturation (5), we investigated whether IL-2 increases Ly49E expression among DETCs as well.…”

“…DETCs and iIELs are both characterized by the expression of several NK receptors, as follows: 2B4 (9, 10), NKG2A/C/E (11), NKG2D (12), and/or members of the Ly49 receptor family (9,11,(13)(14)(15). Among the entire Ly49 receptor family, Ly49E is the only Ly49 member expressed by fetal thymic Vg3 T cells and adult skin DETCs (11), and it is the most abundantly expressed member on TCRgd + iIELs (14).…”

“…Among the entire Ly49 receptor family, Ly49E is the only Ly49 member expressed by fetal thymic Vg3 T cells and adult skin DETCs (11), and it is the most abundantly expressed member on TCRgd + iIELs (14). Whereas the activating NKG2D and 2B4 NK receptors and the inhibitory NKG2A NK receptor are expressed by the majority of DETCs and/or iIELs (9)(10)(11)(12), Ly49E is expressed by only 20 and 10% of DETCs and TCRgd + iIELs, respectively (11,(13)(14)(15). Remarkably, whereas only 20% of DETCs express Ly49E, 60% of their fetal thymic Vg3 + precursors bear the receptor (11).…”

“…Whereas the activating NKG2D and 2B4 NK receptors and the inhibitory NKG2A NK receptor are expressed by the majority of DETCs and/or iIELs (9)(10)(11)(12), Ly49E is expressed by only 20 and 10% of DETCs and TCRgd + iIELs, respectively (11,(13)(14)(15). Remarkably, whereas only 20% of DETCs express Ly49E, 60% of their fetal thymic Vg3 + precursors bear the receptor (11). Similarly, a low percentage of peripheral adult NK cells bears Ly49E, in contrast to their fetal thymic precursors (16)(17)(18).…”