Analysis of HLA-E peptide-binding specificity and contact residues in bound peptide required for recognition by CD94/NKG2.
The MHC class Ib molecule is the primary ligand for /-inhibitory receptors expressed on NK cells， and there is also evidence for -mediated recognition of this molecule. preferentially assembles with a homologous set of derived from the leader sequence of class Ia molecules， but its capacity to bind and present other remains to be fully explored. The motif of was investigated by folding in vitro in the presence of libraries derived from a nonameric sequence randomized at individual anchor positions. A high degree of selectivity was observed at four of five total anchor positions， with preference for amino acids present in -from class Ia leader sequences. Selectivity was also observed at the nonanchor P5 position， with preference for positively charged amino acids， suggesting that electrostatic interactions involving the P5 side chain may facilitate assembly of complexes. The observed motif was strikingly similar to that previously identified for the class Ib molecule， Qa-1. Experiments with tetramers bearing substituted at nonanchor positions demonstrated that P5 and P8 are primary contact residues for interaction with /NKG2 receptors. A conservative replacement of for at P5 completely abrogated to /NKG2. Despite conservation of specificity in and Qa-1， cross-species tetramer-staining experiments demonstrated that the interaction surfaces on /NKG2 and the class Ib ligands have diverged between and .
ABSTRACT A method is presented using electromagnetic pickup probes for RF cavity phase calibration. (We used capacitive style pickup probes.) Pickup probes provide fast readings， and measurements of the phase difference between a pair of pickup probes provides enough information about the phase-energy curve to yield a fit for the zero-crossing phase. We present an overview of the algorithm and measurement results of an implementation on the ReA3 re-accelerator.
目的探讨龙山胃乐胶囊治疗 120例气滞血瘀型胃炎经验。方法龙山胃乐胶囊，口服，一次4～6粒，一日三次。结果痊愈55例，显效32例，好转26例，无效7例，总有效率 94.2%。治疗后与治疗前相比，疗效显著，P0.05。结论总结和探讨龙山胃乐胶囊治疗气滞血瘀型胃炎患者的疗效情况，更加进一步的证实了龙山胃乐胶囊 对治疗消化性溃疡及慢性胃炎气滞血瘀症等症状有显著的疗效。为便于临床应用和更好地开展研究，特提出对龙山胃乐胶囊制剂的研制值得推广和借鉴。
Up-regulation of activating and inhibitory NKG2 receptors in allogeneic and autologous hematopoietic stem cell grafts
BACKGROUND： Hematopoietic Stem Cell Transplantation (HSCT) is known to induce the inhibitory immune receptor NKG2A on NK cells of donor origin. This occurs in allogeneic recipients， in both the haploidentical and HLA-matched settings. METHODS： To gain further insight， not only NKG2A， but also the activating receptors NKG2C and NKG2D were assessed by flow cytometry. Immunophenotyping was carried out not only on CD56(+) but also on CD8(+) lymphocytes from leukemia and lymphoma patients， receiving both HLA-matched (n = 7) and autologous (n = 5) HSCT grafts. Moreover， cognate NKG2 ligands (HLA-E， MICA， ULBP-1， ULBP-2 and ULBP-3) were assessed by immunohistochemistry in diagnostic biopsies from three autotransplanted patients， and at relapse in one case. RESULTS： All the NKG2 receptors were simultaneously up-regulated in all the allotransplanted patients on CD8(+) and/or CD56(+) cells between 30 and 90 days post-transplant， coinciding with， or following， allogeneic engraftment. Up-regulation was of lesser entity and restricted to CD8(+) cells in the autotransplantation setting. The phenotypic expression ratio between activating and inhibitory NKG2 receptors was remarkably similar in all the patients， except two outliers (a long survivor and a short survivor) who surprisingly displayed a similar NKG2 activation immunophenotype. Tumor expression of 2 to 3 out of the 5 tested NKG2 ligands was observed in 3/3 diagnostic biopsies， and 3 ligands were up-regulated post-transplant in a patient. CONCLUSIONS： Altogether， these results are consistent with a dual (activation-inhibition) NK cell re-education mode， an innate-like T cell re-tuning， and a ligand：receptor interplay between the tumor and the immune system following HSCT including， most interestingly， the up-regulation of several activating NKG2 ligands. Turning the immune receptor balance toward activation on both T and NK cells of donor origin may complement ex vivo NK cell expansion/activation strategies in unmanipulated patients.
Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance
A key feature of human natural killer (NK) cells， which enables efficient recognition of infected and malignant target cells， is the expression of HLA class I-specific receptors of the KIR and NKG2 ge
Recognition of Human Histocompatibility Leukocyte Antigen (HLA)-E Complexed with HLA Class I Signal Sequence–derived Peptides by CD94/NKG2 Confers Protection from Natural Killer Cell–mediated Lysis
Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical HLA class I molecule， the gene for which is transcribed in most tissues. It has recently been reported that this molecule binds peptides derived from the signal sequence of HLA class I proteins; however， no function for HLA-E has yet been described. We show that natural killer (NK) cells can recognize target cells expressing HLA-E molecules on the cell surface and this interaction results in inhibition of the lytic process. Furthermore， HLA-E recognition is mediated primarily through the CD94/NKG2-A heterodimer， as CD94-specific， but not killer cell inhibitory receptor (KIR)-specific mAbs block HLA-E-mediated protection of target cells. Cell surface HLA-E could be increased by incubation with synthetic peptides corresponding to residues 3-11 from the signal sequences of a number of HLA class I molecules; however， only peptides which contained a Met at position 2 were capable of conferring resistance to NK-mediated lysis， whereas those having Thr at position 2 had no effect. Interestingly， HLA class I molecules previously correlated with CD94/NKG2 recognition all have Met at residue 4 of the signal sequence (position 2 of the HLA-E binding peptide)， whereas those which have been reported not to interact with CD94/NKG2 have Thr at this position. Thus， these data show a function for HLA-E and suggest an alternative explanation for the apparent broad reactivity of CD94/NKG2 with HLA class I molecules; that CD94/NKG2 interacts with HLA-E complexed with signal sequence peptides derived from "protective" HLA class I alleles rather than directly interacting with classical HLA class I proteins.
正位于湖南湘西北的龙山县，人 口只有58万，少数民族占到66.4%，这个古老平凡的小县城却有着不平凡的故事。2012年稳定的无偿献血队伍达1500余人，2013年无偿献血队伍 高达1805人，千人口献血比例3.11，其中公务员无偿献血人数高达86%。是什么原因让这个湖南最偏远的县城有着和大多数城市不一样的献血热情?带着 满腹期待，笔者坐了7个多小时的汽车，不远千里走近了龙山人民……
Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits.
Abstract CD94 receptors expressed on NK cells have been implicated in the recognition of certain HLA class I allotypes. We now demonstrate that CD94 glycoproteins form disulfide-bonded heterodimers with the NKG2A/B， NKG2C， and NKG2E glycoproteins. NKG2A/B possesses two immunoreceptor tyrosine-based inhibition motif (ITIM) sequences in its cytoplasmic domain， which may be responsible for the inhibitory function of these receptors， whereas other NKG2 proteins lack ITIMs and may potentially transmit positive signals. Structural heterogeneity in the NKG2 gene family and the formation of heterodimers with CD94 provides for the creation of a diverse NK cell repertoire.