Cell-surface expression and alloantigenic function of a human nonclassicalclass I molecule (HLA-E) in transgenic mice

We have introduced the gene (E*01033) encoding the heavy chain of the human nonclassical MHC class I Ag, HLA-E, into the mouse genome. Two founder mic e carry a 21-kb fragment, the others bear an 8-kb fragment. Each of the fou nder mice was mated to mice of an already. established C57BL/10 transgenic line expressing human beta(2)-microglobulin (beta(2)m). Cell surface HLA-E was detected on lymph node cells by how cytometry only in the presence of e ndogenous human beta(2)m. However, HLA-E-reactive mouse CTL. (H-2-unrestric ted) lysed efficiently. the target cells originating from HLA-E transgenic mice without human beta(2)m, showing that the HLA-E protein can be transpor ted to the tell surface in the absence of human beta(2)m, presumably by ass ociation dth murine Plm, Rejection of skin grafts from HLA-E transgenic mic e demonstrates that HLA-E behaves as a transplantation Ag in mice, HLA-E tr ansgenic spleen cells are effective in stimulating an allogeneic CTL respon se in normal and human classical class I (HLA-B27) transgenic mice. Further more, results from split-well analysis indicate that the majority of the pr imary in vivo-induced CTL recognizes HLA-E as an intact molecule (H-2-unres tricted recognition) and not as an HLA-E-derived peptide presented by a mou se MHC molecule, although a small fraction (ranging from 4 to 21%) of the p rimary in vivo-induced CTL is able to recognize HLA-E in an H-2-restricted manner, Based on these observations, we conclude that HLA-E exhibits alloan tigenic properties that are indistinguishable from classical HLA class I mo lecules when expressed in transgenic mice.