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71.
David T. Evans Marian S. Piekarczyk Luis Cadavid Virginia S. Hinshaw D. I. Watkins 《Immunogenetics》1998,47(3):206-211
The products of the highly polymorphic and variable major histocompatibility complex (MHC) class I loci play a crucial role
in host defenses against infectious disease. While similar alleles have been found in closely related species, sharing of
a functional MHC class I allele between two species has never been reported. Here we show that an identical functional MHC
class I molecule is present in two different primate species with an approximate divergence time of 0.7 million years. Lymphocytes
from the red-crested tamarin (Saguinus geoffroyi) expressed an MHC class I allele (Sage-G
*
01) that was identical in coding sequence to an MHC class I allele (Saoe-G
*
08) found in the cotton-top tamarin (Saguinus oedipus). Furthermore, influenza virus-specific cytotoxic T lymphocytes (CTLs) generated in the cotton-top tamarin killed lymphocytes
expressing the influenza virus nucleoprotein (NP) from the red-crested tamarin. Since the influenza virus NP epitope is bound
by Saoe-G*08 in the cotton-top tamarin, it is likely that this molecule is functional in both species. These data provide the first
evidence that functional MHC class I molecules can be maintained entirely intact in two separate species.
Received: 6 June 1997 / Revised: 21 July 1997 相似文献
72.
73.
74.
A yeast artificial chromosome (YAC) contig from the C57BL/6 (H2
b
) mouse was created from the major histocompatibility complex (Mhc, H2 in mouse) class Ib subregion, H2-M. It spans approximately 1.2 megabase (Mb) pairs and unites the previous >1.5-Mb YAC contigs (Jones et al. 1995) into a single
contig, which includes 21 Mhc class I genes distal to H2-T1. A bacterial artificial chromosome (BAC) contig from the 129 (H2
bc
) mouse, spanning approximately 600 kilobases, was also built from Znf173 (Afp, a gene for acid finger protein), through Tctex5 (t-complex testis expressed-5) and Mog (myelin oligodendrocyte glycoprotein), to H2-M2. Twenty-four sequence-tagged site (STS) markers were newly developed, and 35 markers were mapped in the YAC/BAC contigs,
which define the marker order as Cen –Znf173–Tctex5 – Mog–D17Tu42–D17Mit232–H2-M3–D17Leh525–H2-M2– Tel. The gene order of Znf173 – Tctex5 – Mog – D17Tu42 is conserved between mouse and human, showing that the middle H2-M region corresponds to the subregion of the human Mhc surrounding HLA-A.
Received: 25 July 1997 / Revised: 10 September 1997 相似文献
75.
A. G. Grandea III. Paul G. Comber Scott E. Wenderfer Gary Schoenhals Klaus Früh John J. Monaco T. Spies 《Immunogenetics》1998,48(4):260-265
Assembly of major histocompatibility complex (MHC) class I molecules in human cells is dependent on the accessory protein
tapasin, which mediates their interaction with the transporters associated with antigen processing (TAP) and thereby ensures
efficient peptide binding. Analysis of a mouse tapasin complementary DNA defined a conserved polypeptide sharing sequences
diagnostic of a transmembrane protein related to the immunoglobulin superfamily, and an endoplasmic reticulum retention motif.
The mouse tapasin gene was mapped about 70 kilobases from H2-K at the centromeric end of the mouse MHC. Expression of mouse tapasin in a tapasin-deficient human mutant cell line restored
the normal assembly and expression of class I alleles. Thus, tapasin is a structurally and functionally conserved component
of the MHC class I antigen processing pathway. Its genetic linkage to the class I and TAP subunit genes in the MHC may be
of significance in the coordinate expression and functional coadaptation of the diverse gene products.
Received: 1 February 1998 / Revised: 23 March 1998 相似文献
76.
为探讨细胞因子基因(人IL-2、IL-6)转导对于肿瘤细胞膜MHC抗原及细胞膜糖蛋白表达调控的影响,本文利用脂质体介导的方法,将含人IL-6、IL-2基因的逆转录病毒载体分别导入人乳腺癌细胞系MCF-7细胞中,采用间接免疫荧光染色流式细胞仪测定法,对基因转导的瘤细胞细胞膜糖蛋白及MHC抗原表达进行测定。结果表明经两种基因修饰的MCF-7细胞MHCⅠ型抗原表达均获得增强,此外,基因转导细胞可程度不同地表现出细胞膜多种糖蛋白表达的变化。提示肿瘤细胞膜抗原及糖蛋白表达的改变可能是细胞因子基因转导影响肿瘤细胞免疫原性的重要结构基础。 相似文献
77.
J.I. Rodriguez-Barbosa M.C. Ferreras L. Buhler N.D. Jones P. Schneider J.A. Perez-Simon 《MABS-AUSTIN》2018,10(7):1030-1044
Natural killer (NK) cells are a population of innate type I lymphoid cells essential for early anti-viral responses and are known to modulate the course of humoral and cellular-mediated T cell responses. We assessed the role of NK cells in allogeneic CD8 T cell-mediated responses in an immunocompetent mouse model across an MHC class I histocompatibility barrier to determine its impact in therapeutic clinical interventions with polyclonal or monoclonal antibodies (mAbs) targeting lymphoid cells in transplantation. The administration of an NK cell depleting antibody to either CD8 T cell replete or CD8 T cell-depleted naïve C57BL/6 immunocompetent mice accelerated graft rejection. This accelerated rejection response was associated with an in vivo increased cytotoxic activity of CD8 T cells against bm1 allogeneic hematopoietic cells and bm1 skin allografts. These findings show that NK cells were implicated in the control host anti-donor cytotoxic responses, likely by competing for common cell growth factors in both CD8 T cell replete and CD8 T cell-depleted mice, the latter reconstituting in response to lymphopenia. Our data calls for precaution in solid organ transplantation under tolerogenic protocols involving extensive depletion of lymphocytes. These pharmacological biologics with depleting properties over NK cells may accelerate graft rejection and promote aggressive CD8 T cell cytotoxic alloresponses refractory to current immunosuppression. 相似文献
78.
D. Bellavia L. Raimondi V. Costa A. De Luca V. Carina M. Maglio M. Fini R. Alessandro G. Giavaresi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):1893-1901
Background
Exosomes are nanovesicles actively secreted by potentially all cell types, including tumour cells, with the primary role of extracellular systemic communication mediators, both at autocrine and paracrine levels, at short and long distances. Recently, different studies have used exosomes as a delivery system for a plethora of different molecules, such as drugs, microRNAs and proteins. This has been made possible thanks to the simplicity in exosomes engineering, their great stability and versatility for applications in oncology as well as in regenerative medicine.Scope of review
The aim of this review is to provide information on the state-of-the-art and possible applications of engineered exosomes, both for cargo and specific cell-targeting, in different pathologies related to the musculoskeletal system.Major conclusions
The use of exosomes as therapeutic agents is rapidly evolving, different studies explore drug delivery with exosomes using different molecules, showing an enormous potential in various research fields such as oncology and regenerative medicine.General significance
However, despite the significant progress made by the different studies carried out, currently, the use of exosomes is not a therapeutic reality for the considerable difficulties to overcome. 相似文献79.
Tracy A. Stone Gregory B. Cole Huong Q. Nguyen Simon Sharpe Charles M. Deber 《Bioorganic & medicinal chemistry》2018,26(6):1189-1196
Cyclization has been recognized as a valuable technique for increasing the efficacy of small molecule and peptide therapeutics. Here we report the application of a hydrocarbon staple to a rationally-designed cationic antimicrobial peptide (CAP) that acquires increased membrane targeting and interaction vs. its linear counterpart. The previously-described CAP, 6K-F17 (KKKKKK-AAFAAWAAFAA-NH2) was used as the backbone for incorporation of an i to i?+?4 helical hydrocarbon staple through olefin ring closing metathesis. Stapled versions of 6K-F17 showed an increase in non-selective membrane interaction, where the staple itself enhances the degree of membrane interaction and rate of cell death while maintaining high potency against bacterial membranes. However, the higher averaged hydrophobicity imparted by the staple also significantly increases toxicity to mammalian cells. This deleterious effect is countered through stepwise reduction of the stapled 6K-F17’s backbone hydrophobicity through polar amino acid substitutions. Circular dichroism assessment of secondary structure in various bacterial membrane mimetics reveals that a helical structure may improve – but is not an absolute requirement for – antimicrobial activity of 6K-F17. Further, phosphorus-31 static solid state NMR spectra revealed that both non-toxic stapled and linear peptides bind bacterial membranes in a similar manner that does not involve a detergent-like mechanism of lipid removal. The overall results suggest that the technique of hydrocarbon stapling can be readily applied to membrane-interactive CAPs to modulate how they interact and target biological membranes. 相似文献
80.
Jong Cheol Lee Se Mi Park Il Yong Kim Hyerim Sung Je Kyung Seong Myeong Hee Moon 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(9):980-990
Given their important role in neuronal function, there has been an increasing focus on altered lipid levels in brain disorders. The effect of a high-fat (HF) diet on the lipid profiles of the cortex, hippocampus, hypothalamus, and olfactory bulb of the mouse brain was investigated using nanoflow ultrahigh pressure liquid chromatography-electrospray ionization-tandem mass spectrometry in the current study. For 8?weeks, two groups of 5-week-old mice were fed either an HF or normal diet (6 mice from each group analyzed as the F and N groups, respectively). The remaining mice in both groups then received a 4-week normal diet. Each group was then subdivided into two groups for another 4-week HF or normal diet. Quantitative analysis of 270 of the 359 lipids identified from brain tissue revealed that an HF diet significantly affected the brain lipidome in all brain regions that were analyzed. The HF diet significantly increased diacylglycerols, which play a role in insulin resistance in all regions that were analyzed. Although the HF diet increased most lipid species, the majority of phosphatidylserine species were decreased, while lysophosphatidylserine species, with the same acyl chain, were substantially increased. This result can be attributed to increased oxidative stress due to the HF diet. Further, weight-cycling (yo-yo effect) was found more critical for the perturbation of brain lipid profiles than weight gain without a preliminary experience of an HF diet. The present study reveals systematic alterations in brain lipid levels upon HF diet analyzed either by lipid class and molecular levels. 相似文献