Article

HLA-F is a surface marker on activated lymphocytes

The Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle,WA 98109-1024,USA.
European Journal of Immunology (Impact Factor: 4.52). 08/2010; 40(8):2308-18. DOI: 10.1002/eji.201040348
Source: PubMed

ABSTRACT Of the three nonclassical class I antigens expressed in humans, HLA-F has been least characterized with regard to expression or function. In this study, we examined HLA-F expression focusing on lymphoid cells, where our previous work with homologous cell lines had demonstrated surface HLA-F expression. HLA-F protein expression was observed by Western blot analysis in all resting lymphocytes, including B cells, T cells, NK cells, and monocytes, all of which lacked surface expression in the resting state. Upon activation, using a variety of methods to activate different lymphocyte subpopulations, all cell types that expressed HLA-F intracellularly showed an induction of surface HLA-F protein. An examination of peripheral blood from individuals genetically deficient for TAP and tapasin expression demonstrated the same activation expression profiles for HLA-F,but with altered kinetics post-activation. Further analysis of CD41+CD25+1 Treg showed that HLA-F was not upregulated on the major fraction of these cells when they were activated,whereas CD41+CD25- T cells showed strong expression of surface HLA-F when activated under identical conditions. These findings are discussed with regard to possible functions for HLA-F and its potential clinical use as a marker of an activated immune response.

0 Followers
 · 
104 Views
 · 
2 Downloads
  • Source
    • "To our knowledge, this is the first demonstration in which sHLA-F is present in biological samples. Lee et al. have shown that this molecule is expressed on the surface of lymphocytes upon activation [23]. Since HLA-Ib molecules are generally released as soluble molecules through shedding mediated by metalloproteases [24], it can be envisaged that the presence of plasma sHLA-F may be related to the immune system activation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS) of neuroblastoma (NB) patients. Concentration of soluble (s) biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3) or serum (calprotectin) samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient's outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS), whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.
    11/2013; 2013:956878. DOI:10.1155/2013/956878
  • Source
    • "Additionally, its expression can confer resistance to NK cell-mediated lysis [19,20]. HLA-F has been recently reported to be a surface marker for activated lymphocytes [21], while HLA-G has its highest expression during pregnancy and is thought to play a key role in modulating immune tolerance [22]. There is a recently published study by Prigione et al. that reports a lower concentration of soluble HLA-G in sera may predispose to JIA and soluble HLA-E concentration in synovial fluid correlated with the number of affected joints [23]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis that progresses to destruction of cartilage and bone. Bone marrow (BM) cells have been shown to contribute to this pathogenesis. In this study, we compared differentially expressed molecules in BM cells from RA and osteoarthritis (OA) patients and analyzed abnormal regulatory networks to identify the role of BM cells in RA. Gene expression profiles (GEPs) in BM-derived mononuclear cells from 9 RA and 10 OA patients were obtained by DNA microarray. Up- and down-regulated genes were identified by comparing the GEPs from the two patient groups. Bioinformatics was performed by Expression Analysis Systemic Explorer (EASE) 2.0 based on gene ontology, followed by network pathway analysis with Ingenuity Pathways Analysis (IPA) 7.5. The BM mononuclear cells showed 764 up-regulated and 1,910 down-regulated genes in RA patients relative to the OA group. EASE revealed that the gene category response to external stimulus, which included the gene category immune response, was overrepresented by the up-regulated genes. So too were the gene categories signal transduction and phosphate metabolism. Down-regulated genes were dominantly classified in three gene categories: cell proliferation, which included mitotic cell cycle, DNA replication and chromosome cycle, and DNA metabolism. Most genes in these categories overlapped with each other. IPA analysis showed that the up-regulated genes in immune response were highly relevant to the antigen presentation pathway and to interferon signaling. The major histocompatibility complex (MHC) class I molecules, human leukocyte antigen (HLA)-E, HLA-F, and HLA-G, tapasin (TAP) and TAP binding protein, both of which are involved in peptide antigen binding and presentation via MHC class I molecules, are depicted in the immune response molecule networks. Interferon gamma and interleukin 8 were overexpressed and found to play central roles in these networks. Abnormal regulatory networks in the immune response and cell cycle categories were identified in BM mononuclear cells from RA patients, indicating that the BM is pathologically involved in RA.
    Arthritis research & therapy 06/2011; 13(3):R89. DOI:10.1186/ar3364 · 3.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiac rehabilitation is one of the most effective treatments for secondary prevention for patients with heart disease. In particular, exercise training confers a variety of clinical benefits that leads to an increase in functional ability and a decrease in mortality in patients with a variety of cardiac diagnoses. Although they require a long-term commitment, standard training programs are safe and cost-effective. Despite its proven benefit, however, cardiac rehabilitation is underused in the United States.
    Physical Medicine and Rehabilitation Clinics of North America 11/2009; 20(4):719-36. DOI:10.1016/j.pmr.2009.06.006 · 1.09 Impact Factor
Show more

Preview

Download
2 Downloads