We previously showed that the availability of a nonamer peptide derived from certain HLA class I signal sequences is a necessary requirement for the stabilization of endogenous HLA-E expression on the surface of 721.221 cells. This led us to examine the ability of HLA-E to protect HLA class I transfectants from natural killer (NK) cell-mediated lysis. It was possible to implicate the CD94͞NKG2A complex as an inhibitory receptor recognizing this class Ib molecule by using as target a .221 transfectant selectively expressing surface HLA-E. HLA-E had no apparent inhibitory effect mediated through the identified Ig superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2͞LIR1. Further studies of CD94͞NKG2؉ NK cell-mediated recognition of .221 cells transfected with different HLA class I allotypes (i.e., -Cw4, -Cw3, -B7) confirmed that the inhibitory interaction was mediated by CD94͞NKG2A recognizing the surface HLA-E molecule, because only antibodies directed against either HLA-E, CD94, or CD94͞NKG2A specifically restored lysis. Surface stabilization of HLA-E in cold-treated .221 cells loaded with appropriate peptides was sufficient to confer protection, resulting from recognition of the HLA class Ib molecule by the CD94͞NKG2A inhibitory receptor. Consistent with the prediction that the ligand for CD94͞NKG2A is expressed ubiquitously, our examination of HLA-E antigen distribution indicated that it is detectable on the surface of a wide variety of cell types.

The human antimicrobial peptide LL-37 plays an important role in host defense against infection. In addition to its antimicrobial action, other activities have been described in eukaryotic cells that may contribute to the healing response. In this study, we demonstrated that in vitro human cathelicidin activates migration of the human keratinocyte cell line HaCaT, involving phenotypic changes related to actin dynamics and associated to augmented tyrosine phosphorylation of proteins involved in focal adhesion complexes, such as focal adhesion kinase and paxillin. Other events involved in the LL-37 response were the induction of the Snail and Slug transcription factors, activation of matrix metalloproteinases and activation of the mitogen-activated protein kinase , and phosphoinositide 3-kinase/Akt signaling pathways. These signaling events could be mediated not only through the transactivation of EGFR but also through the induction of G-protein-coupled receptor FPRL-1 expression in these cells. Finally, by in vivo adenoviral transfer of the antimicrobial peptide to excisional wounds in ob/ob mice, we demonstrated that LL-37 significantly improved re-epithelialization and granulation tissue formation. The protective and regenerative activities of LL-37 support its therapeutic potential to promote wound healing.