The accumulation of protein aggregates is toxic and linked to different diseases such as neurodegenerative disorders, but the role of the immune system to target and destroy aggregate-carrying cells is still relatively unknown. Here we show a substrate-specific presentation of antigenic peptides to the direct MHC class I pathway via autophagy. We observed no difference in presentation of peptides derived from the viral EBNA1 protein following suppression of autophagy by knocking down Atg5 and Atg12. However, the same knock down treatment suppressed the presentation from ovalbumin. Fusing the aggregate-prone poly-glutamine (PolyQ) to the ovalbumin had no effect on antigen presentation via autophagy. Interestingly, fusing the EBNA1-derived gly-ala repeat (GAr) sequence to ovalbumin rendered the presentation Atg5/12 independent. We also demonstrate that the relative levels of protein expression did not affect autophagy-mediated antigen presentation. These data suggest a substrate-dependent presentation of antigenic peptides for the MHC class I pathway via autophagy and indicate that the GAr of the EBNA1 illustrates a novel virus-mediated mechanism for immune evasion of autophagy-dependent antigen presentation.

• MeSH
• antigeny MeSH
• autofagie MeSH
• histokompatibilita - antigeny třídy I * MeSH
• histokompatibilita - antigeny třídy II metabolismus   MeSH
• imunitní únik MeSH
• ovalbumin MeSH
• prezentace antigenu * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The autoimmune regulator (Aire) serves an essential function for T cell tolerance by promoting the "promiscuous" expression of tissue antigens in thymic epithelial cells. Aire is also detected in rare cells in peripheral lymphoid organs, but the identity of these cells is poorly understood. Here, we report that Aire protein-expressing cells in lymph nodes exhibit typical group 3 innate lymphoid cell (ILC3) characteristics such as lymphoid morphology, absence of "classical" hematopoietic lineage markers, and dependence on RORγt. Aire+ cells are more frequent among lineage-negative RORγt+ cells of peripheral lymph nodes as compared with mucosa-draining lymph nodes, display a unique Aire-dependent transcriptional signature, express high surface levels of MHCII and costimulatory molecules, and efficiently present an endogenously expressed model antigen to CD4+ T cells. These findings define a novel type of ILC3-like cells with potent APC features, suggesting that these cells serve a function in the control of T cell responses.

• MeSH
• adhezní molekula epiteliálních buněk metabolismus   MeSH
• antigen prezentující buňky imunologie   MeSH
• antigeny CD11 metabolismus   MeSH
• fenotyp MeSH
• genetická transkripce MeSH
• histokompatibilita - antigeny třídy II metabolismus   MeSH
• jaderné receptory - podrodina 1, skupina F, člen 3 metabolismus   MeSH
• lymfatické uzliny cytologie   MeSH
• lymfocyty imunologie   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši knockoutované MeSH
• myši MeSH
• přirozená imunita MeSH
• regulace genové exprese MeSH
• transkripční faktory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Monocytes represent a heterogeneous population of cells subdivided according to the expression level of membrane antigens. A pro-inflammatory (intermediate/nonclassical) subpopulation of monocytes is defined by expression of CD16. CD163 seems to be characteristically preferentially expressed by immunosuppressive monocytes. The aim of our study was to evaluate the distribution of monocyte subpopulations in 71 patients with kidney allograft transplantation. RESULTS: The phenotype was evaluated by flow cytometry in defined time points. The proportions of peripheral CD14+CD16+ monocytes were downregulated immediately after the kidney transplantation and basiliximab treatment partially attenuated this trend. The transient downregulation of the CD14+CD16+ subpopulation was adjusted to basal values in two months. The proportions of CD14+CD163+ monocytes were transiently upregulated early after the kidney transplantation and remained higher during the first month in most patients. In ATG treated patients, the expansion of CD14+CD163+ monocytes was delayed but their upregulation lasted longer. In vitro data showed the direct effect of ATG and methylprednisolone on expression of CD16 and CD163 molecules while basiliximab did not affect the phenotype of cultured monocytes. CONCLUSIONS: We assume from our data that kidney allograft transplantation is associated with modulation of monocyte subpopulations (CD14+CD16+ and CD14+CD163+) partially affected by an immunosuppressive regime used.

• MeSH
• antigeny CD14 metabolismus   MeSH
• antigeny CD36 metabolismus   MeSH
• antigeny diferenciační B-lymfocytární metabolismus   MeSH
• antigeny diferenciační myelomonocytární metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• dospělí MeSH
• fenotyp MeSH
• histokompatibilita - antigeny třídy II metabolismus   MeSH
• homologní transplantace MeSH
• imunofenotypizace MeSH
• imunosupresiva farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monocyty účinky léků   imunologie   metabolismus   MeSH
• přežívání štěpu imunologie   MeSH
• průtoková cytometrie MeSH
• receptory buněčného povrchu metabolismus   MeSH
• receptory IgG metabolismus   MeSH
• rejekce štěpu imunologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• transplantace ledvin * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES AND DESIGN: We determined in a rat model (1) the presence and dynamics of alloantibodies recognizing MHC complexes on quiescent Brown-Norway (BN) splenic cells in the sera of Lewis (LEW) recipients of Brown-Norway iliolumbar vein grafts under tacrolimus immunosuppression; and (2) the presence of immunoglobulins in the wall of acute rejected vein allografts. MATERIALS AND METHODS: Flow cytometry was used for the analysis of day 0, 14 and 30 sera obtained from Lewis recipients of isogeneic iliolumbar vein grafts (group A) or Brown-Norway grafts (group B, C) for the presence of donor specific anti-MHC class I and II antibodies. Tacrolimus 0.2 mg/kg daily was administered from day 1 to day 30 (group C). Histology was performed on day 30. RESULTS: Sera obtained preoperatively and on day 30 were compared in all groups. The statistically significant decrease of anti MHC class I and II antibody binding was observed only in allogenic non-immunosuppressed group B (splenocytes: MHC class I - day 0 (93% ± 7% ) vs day 30 (66% ± 7%), p = 0.02, MHC class II - day 0 (105% ± 3% ) vs day 30 (83% ± 5%), p = 0.003; B-cells: MHC class I - day 0 (83% ± 5%) vs day 30 (55% ± 6%), p = 0.003, MHC class II - day 0 (101% ± 1%) vs day 30 (79% ± 6%), p = 0.006; T-cells: MHC class I - day 0 (71% ± 7%) vs day 30 (49% ± 5%), p = 0.04). No free clusters of immunoglobulin G deposition were detected in any experimental group. CONCLUSION: Arterialized venous allografts induce strong donor-specific anti-MHC class I and anti-MHC class II antibody production with subsequent immune-mediated destruction of these allografts with no evidence of immunoglobulin G deposition. Low-dose tacrolimus suppress the donor-specific antibody production.

• MeSH
• alografty imunologie   MeSH
• arterie transplantace   MeSH
• buněčná cytotoxicita závislá na protilátkách účinky léků   imunologie   MeSH
• časové faktory MeSH
• histokompatibilita - antigeny třídy I imunologie   metabolismus   MeSH
• histokompatibilita - antigeny třídy II imunologie   metabolismus   MeSH
• imunosupresivní léčba * MeSH
• isoprotilátky imunologie   MeSH
• krysa rodu rattus MeSH
• podskupiny lymfocytů imunologie   metabolismus   MeSH
• rejekce štěpu farmakoterapie   imunologie   MeSH
• slezina cytologie   imunologie   metabolismus   MeSH
• transplantační imunologie MeSH
• vény imunologie   transplantace   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In the recent past, it has repeatedly been reported that CD4 cells play an important role in the immunology of chronic myeloid leukaemia. It was therefore of interest to test their activity in an animal model using bcr-abl-transformed cells. BALB/c mice were four times immunized with a DNA vaccine carrying the bcr-abl fusion gene. Two weeks after the last vaccine dose, the animals were challenged with syngeneic bcr-abl-transformed 12B1 cells which form solid tumors after subcutaneous administration. At the time of challenge, animals were treated with antibodies against the CD8+ T cells or CD4+ T cells. The efficacy of the depletion was monitored and found highly effective. All nonimmunized animals developed tumors. All animals untreated with the antibodies as well as those in which CD8+ T cells had been depleted, were fully protected against the challenge. On the other hand, almost all mice treated with anti-CD4+ antibody developed tumors. These results strongly suggested that the CD4+ T cells acted as effectors in the present system.

• MeSH
• antigeny CD95 imunologie   metabolismus   MeSH
• bcr-abl fúzové proteiny genetika   imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• CD8-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• DNA vakcíny imunologie   MeSH
• histokompatibilita - antigeny třídy II imunologie   metabolismus   MeSH
• imunizace MeSH
• lidé MeSH
• ligand Fas metabolismus   MeSH
• lymfocytární deplece MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nádorová transformace buněk genetika   imunologie   MeSH
• nádory genetika   imunologie   mortalita   prevence a kontrola   MeSH
• protinádorové vakcíny genetika   imunologie   MeSH
• slezina cytologie   imunologie   MeSH
• transformované buněčné linie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Formation of the immunological synapse between an antigen-presenting cell (APC) and a T cell leads to signal generation in both cells involved. In T cells, the lipid raft-associated transmembrane adaptor protein LAT plays a central role. Its phosphorylation is a crucial step in signal propagation, including the calcium response and mitogen-activated protein kinase activation, and largely depends on its association with the SLP76 adaptor protein. Here we report the discovery of a new palmitoylated transmembrane adaptor protein, termed SCIMP. SCIMP is expressed in B cells and other professional APCs and is localized in the immunological synapse due to its association with tetraspanin-enriched microdomains. In B cells, it is constitutively associated with Lyn kinase and becomes tyrosine phosphorylated after major histocompatibility complex type II (MHC-II) stimulation. When phosphorylated, SCIMP binds to the SLP65 adaptor protein and also to the inhibitory kinase Csk. While the association with SLP65 initiates the downstream signaling cascades, Csk binding functions as a negative regulatory loop. The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions.

• MeSH
• adaptorové proteiny signální transdukční chemie   metabolismus   MeSH
• aktivace lymfocytů MeSH
• antigen prezentující buňky imunologie   MeSH
• B-lymfocyty imunologie   metabolismus   MeSH
• fosfoproteiny metabolismus   MeSH
• HEK293 buňky MeSH
• histokompatibilita - antigeny třídy II imunologie   metabolismus   MeSH
• imunologické synapse chemie   MeSH
• lidé MeSH
• malá interferující RNA MeSH
• membránové mikrodomény chemie   metabolismus   MeSH
• membránové proteiny chemie   genetika   imunologie   metabolismus   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• prezentace antigenu MeSH
• RNA interference MeSH
• sekvence aminokyselin MeSH
• signální transdukce MeSH
• skupina kinas odvozených od src-genu metabolismus   MeSH
• src homologní domény MeSH
• T-lymfocyty imunologie   MeSH
• tyrosinkinasy chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• buněčné linie MeSH
• histokompatibilita - antigeny třídy I metabolismus   MeSH
• histokompatibilita - antigeny třídy II metabolismus   MeSH
• metastázy nádorů patologie   MeSH
• myši MeSH
• Papillomaviridae genetika   MeSH
• rekombinantní DNA MeSH
• virová transformace buněk MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

• MeSH
• B-lymfocyty cytologie   metabolismus   ultrastruktura   MeSH
• dendritické buňky imunologie   metabolismus   ultrastruktura   MeSH
• exprese genu MeSH
• histokompatibilita - antigeny třídy II genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• makrofágy cytologie   metabolismus   ultrastruktura   MeSH
• omentum MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH