Cells were stimulated with different concentrations of GPC81–95 peptide (1, 5 and 10 μg/ml) and cultured in the presence or absence of TLR1–9 ligands and the expression

levels of membrane-bound LAP (TGF-β1) were analysed using flow cytometry. None of TLR ligands, including LPS, increased the expression of LAP (TGF-β1) on GPC81–95 peptide-stimulated T cells (data not shown). Anti-CD3 antibody induces LAP (TGF-β1) on T cells and suppresses inflammatory condition in a TGF-β1-dependent manner.3 Moreover, it has been shown that vascular endothelial growth factor (VEGF) induces TGF-β1.20 To compare the ability of these ligands with GPC81–95 to induce LAP (TGF-β1), PBMCs were stimulated with different concentrations of anti-CD3 antibody, VEGF, VIP, PMA/ionomycin, staphylococcal enterotoxin B, purified protein Roxadustat chemical structure derivative or GPC81–95 and the percentage of LAP (TGF-β1)+ CD4+ T cells was analysed using flow cytometry. GPC81–95 and anti-CD3 antibody (1 and 5 μg/ml) induced LAP (TGF-β1) on CD4 T cells,

whereas VEGF, VIP, PMA/ionomycin, staphylococcal enterotoxin B and purified protein derivative did not induce LAP (TGF-β1) expression (Fig. 3e). Apoptotic cells are known to produce TGF-β1.21 To determine whether Hydroxychloroquine in vitro peptide-induced LAP (TGF-β) expression on CD4+ T cells is the result of T-cell apoptosis, CD4+ Jurkat T cells were treated with different concentrations of GPC81–95 peptide (5–30 μg/ml). The percentages of cell death and early apoptosis were analysed by 7-AAD and annexin Immune system V staining, respectively, 5 and 24 hr after exposure. GPC81–95 did not induce cell death or apoptosis in Jurkat T cells (Fig. 4a). All the assays were performed in triplicate and the results were confirmed in two independent experiments. Moreover, peptide-induced LAP (TGF-β1)+ CD4+ Jurkat T cells were 7-AAD− annexin

V−, demonstrating that these cells are not dead or dying (Fig. 4b,c). The PBMCs isolated from healthy donors were cultured with GPC81–95 or an irrelevant peptide (AFP365–373) and then stimulated with 10 ng/ml LPS. The concentrations of different pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and RANTES) were measured in the supernatant after 24 hr (Fig. 5a). Treatment of the cells with an irrelevant peptide (AFP365–373) did not alter the concentration of pro-inflammatory cytokines in comparison with non-treated cells or cells treated with PBS diluents (data not shown), suggesting that the irrelevant peptide has no inhibitory effect. In contrast, GPC81–95-treatment inhibited the production of TNF-α but not the production of IL-1β, IL-6 or RANTES (Fig. 5a). The average percentages of inhibition from four independent experiments are shown in Fig. 5(b), demonstrating that TNF-α is the only pro-inflammatory cytokine measured that was consistently inhibited by GPC81–95 treatment (AFP365–373 was used as an irrelevant peptide). Inhibition of TNF-α by GPC81–95 treatment was seen over a range of LPS doses (Fig. 5c).

After the immunizing infection, the key experimental immunized-challenged group was rested for 4 weeks to enable the mucosa to recover, before being challenged with a low-dose secondary infection. Our hypothesis is that challenged animals should respond with a considerably more vigorous intestinal inflammatory response than that evident during primary exposure, and to enable this

to be quantified accurately against baseline values of each of the parameters that we measured, we included four carefully chosen control groups. The strain of A. ceylanicum used was that maintained at the University of Nottingham since 1984, originally acquired from Dr. Rajasekariah of Hindustan CIBA-Geigy Ltd., Bombay, India. It is believed to be of dog origin. The methods employed for maintenance of the parasite, for worm recovery and faecal egg counts have all been described previously in full (16,19). Worms were EPZ-6438 nmr removed from infected animals by treatment with ivermectin (‘Ivomec super’ MSD AGVET, Division of Merk Sharp and Dohme Limited, Holland). A stock concentration of 200 μg/mL drug was made by a 1 in 50 dilution using distilled water and this was used to treat at 200 μg/kg body weight. The Golden hamsters (DSN strain) used in this study were originally obtained from Harlan Olac in 1983 and since then maintained

in the animal house of the School of Biology as a closed colony. Only female hamsters were used

in this experiment. Animals were kept under conventional animal house conditions. Pelleted food and tap water were supplied Selleck Ponatinib ad libitum. Cages were cleaned twice a week to prevent re-infection. Animals were first weighed 1 or 2 weeks before infection and thereafter twice a week until the completion of each experiment. As the colony was maintained under conventional animal house conditions, the animals were exposed to various micro-organisms present in the environment. To prepare hamsters for infection and reduce other competing intestinal micro-organisms, all animals were pre-treated for 1 week with Emtryl (May & Baker, Dimetridazole at a concentration of 1 g/L in drinking water), then for another week with Terramycin (Pfizer, oxytetracycline hydrochloride, 3 g/L in drinking crotamiton water) and were returned to normal drinking water for 1 week prior to infection. Animals were used at approximately 8–12 weeks of age. The methods used to measure the height of villi, the depth of the Crypts of Lieberkühn and mitotic activity were described comprehensively by Alkazmi et al. (20). Methods for assessing the mast cell, goblet cell, eosinophil and Paneth cell responses were reported earlier in full (18). In all the histological observations reported here, we counted cells/mm2 of mucosal tissue on appropriately stained sections, using the Weible 2 graticule as described by Kermanizadeh et al. (29).

The transcription factor FoxP3 has been described as the most specific molecular marker for Treg[25,26]. We therefore analysed FoxP3 expression Midostaurin nmr in CD4+CD25high T cells isolated from cancer patients and healthy donors using real-time PCR. As depicted in Fig. 4a, CD4+CD25high T lymphocytes from both cancer patients and healthy donors expressed

similar high levels of FoxP3. Together, these results indicated that CD4+CD25high T cells isolated from patients demonstrated specific phenotypic features of immunosuppressive regulatory T cells. Furthermore, no phenotypic difference was observed on the CD4+CD25high T cells from cancer patients or healthy donors. We sought to compare the functional status of sorted CD4+CD25high T cells from cancer patients and healthy controls. Quantitative analysis of the regulatory function of CD4+CD25high T cells was performed by co-culturing them with autologous T responder cells at different ratios. CD4+CD25high cells from the PBMCs or TILs were anergic to this stimulation and the proliferation of CD4+CD25– T cells induced by anti-CD3 and anti-CD28 was reduced in the presence of CD4+CD25high T lymphocytes. Increasing the ratio of CD4+CD25–/CD4+CD25high T cells resulted in less suppression. No significant differences were detected between cancer patients and healthy controls

under the conditions we tested (Fig. 4b). We also analysed the concentrations of cytokines in the supernatants obtained from the co-culture Selleckchem EPZ6438 of CD4+CD25high T cells and CD4+CD25–T cells. As shown in Fig. 4c, CD4+CD25– T cells cultured alone produced large amounts of IFN-γ from both healthy controls and cancer patients. Supernatants from cultures of CD4+CD25high

T cells alone with APCs contained few IFN-γ. Co-culture of CD4+CD25high T cells with CD4+CD25– T cells at a 1:1 ratio resulted in significant inhibition of IFN-γ secretion in the culture supernatants from healthy controls and cancer patients. This suppressive effect was Edoxaban not significantly different between CD4+CD25high from cancer patients and those from healthy donors. The results indicated that CD4+CD25high T cells isolated from patients or healthy donors showed a conventional phenotype and equal ability to suppress the proliferation and cytokine secretion of CD4+ effector T cells, thereby allowing identification of these cells as Treg. The percentage of Treg cells in the CD4+ population from the PBMCs in healthy controls or bladder carcinoma patients was evaluated. Our data showed that the patients with bladder carcinoma had a significantly higher Treg frequency in the PBMCs [8·7% ± 5·4% (range: 2·4–15·5%); n = 45] compared with healthy controls [2·4% ± 1·0% (range: 1·1–4·2%); n = 20] (Fig. 5a and b). The proportion of Treg cells in tumour tissue from patients with bladder carcinoma (n = 20) was also examined. As shown in Fig.

The homeostasis of the fibrinolytic system is finely regulated

by plasminogen activators such as t-PA, and natural inhibitors such as PAI-1 and TAFI. It is thought that t-PA plays a relevant role in initiating fibrinolysis and thrombolysis. The high circulating levels of t-PA antigen in patients with active BP do not conflict with the reduction in fibrinolysis because the t-PA immunoassay largely measures circulating complexes of t-PA and PAI-1. Consequently, increased concentrations of t-PA antigen provide indirect information concerning PAI-1 expression and indicate reduced rather than increased fibrinolysis [24]. The inhibition of fibrinolysis may have important effects on systemic circulation; high plasma www.selleckchem.com/products/R788(Fostamatinib-disodium).html PAI-1 levels are generally considered to be a cardiovascular risk factor [25]. Clinical and experimental evidence suggests that the long-term effects of PAI-1 are crucial factors in the occurrence of thrombotic events. The increased risk of cardiovascular events in BP can therefore be attributed partially to the inhibition of fibrinolytic system, which may act synergistically with the previously demonstrated increased activation of blood coagulation associated with the disease

[4, 9, 12]. Buparlisib molecular weight Another factor possibly contributing to the increased risk of thrombosis in BP is the presence of anti-phospholipid antibodies, which have been detected in about 20% of cases in a series of 28 patients with this disease [26]. The possible influence on our results of comorbidities such as hyperthyroidism and diabetes, which may impair the fibrinolytic

process [27, 28], has also been considered. None of our patients had thyroid dysfunction Baricitinib and the alterations of fibrinolysis and coagulation were evident even after the exclusion of the three diabetic patients. Activation of the coagulation system has local effects on the skin (by contributing to inflammation, tissue damage and blister formation) and systemic effects on the blood stream that increase thrombotic risk [10, 11]. At local level, it has been demonstrated that the fibrinolytic system is activated in blister fluid taken from BP patients [21] and plays a critical role in blister formation in experimental BP by mediating the physiological activation of metalloproteinase-9 [23]. Moreover, in a model of cultured human keratinocytes, stimulation with antibodies to human BP180 led to high levels of tPA expression and release [22]. Our previous data [4, 9] confirm the involvement of fibrinolysis activation and coagulation activation in human BP blister fluid, as shown by high levels of d-dimer (a marker of fibrin degradation) and prothrombin fragment F1+2 (a marker of thrombin generation). At systemic level, the increase in PAI-1 levels indicates that fibrinolysis is inhibited in BP.

[5, 7] At the same time that urodynamics is recognized

as the most proper tool to evaluate voiding dysfunctions, training on it was deemed insufficient in many surveyed academic centers with almost 50% of the doctors referring to the training as inadequate or insufficient.[6, 8] Alarmingly, in the US only 20% of residents could recall formal training of the exam.[9] A minimum of 30 exams per year was recommended by Minimum Standards for Urodynamic practice in the UK but it is not evidence-based. Our fellowship provides a remarkably higher number enabling the fellows to experience intense exposure Panobinostat research buy that may change the conceptualization on the use of this tool to appropriately treat BPH patients.[10] Our study analyzed two groups of urologists with different ICG-001 clinical trial times of exposition to urodynamic studies and both significantly improved their capacity in doing, interpreting and understanding the importance of the exam as a unique tool to evaluate voiding dysfunctions. As in other surveys, we demonstrated that urodynamic usage for BPH is related to the availability of the exam as well as the reliance on the person performing the test. As in the survey from Canada utilization of urodynamic test prior

to stress urinary incontinence (SUI) operations was related to the availability of the testing in the city or evaluated surgeon’s hospital, meaning that 54% of the surgeons would always Docetaxel datasheet demand the exam but only 5% of the gynecologists who do not readily have it.[11] In the same manner, a multi-institutional study showed that many gynecologists do not use urodynamic investigations as plainly recognized with higher rates of utilization for subspecialists (72% using cystometries against 44% of general gynecologists) despite having easy access to the test. These observations may be related to the lack of recognition on the importance of urodynamic evaluation in prognostic results as well as poor understanding of the information derived from the test.[12] Our data also suggests that senior

urologists are more prone to disregard the results depending on who did the exam adding another factor of incredulity to the reasons doctors disregard the exam. However, our study showed that after being exposed to the urodynamic concepts, 90% of the professionals would order the exam for all patients considered to TURP, translating the recognition of the importance of the exam for further urological treatment in opposition to the Canadian survey that revealed that 91% of the urologists would never or rarely do urodyamics for HBP, with 69% of them doing TURP based solely on symptoms.[3] In the same way, it was astonishing that many urologists still perform cystoscopy more often than urodynamics for voiding dysfunctions as demonstrated in a regional US survey.

In addition, FEZ1 plays a role in cell polarization and axonal initiation [24]. FEZ1 has been shown to interact with selleck screening library tubulin and kinesin motor proteins and to control the movement of mitochondria within the growing neurites of PC12 cells stimulated by nerve growth factor [25]. In rats, FEZ1 mRNA is abundantly expressed in early stages of the developing brain at the onset of neurogenesis [26]. In particular, abundant FEZ1 expression is found in neurones of the olfactory bulb, cortex and hippocampus of the adult rat brain but not in oligodendrocytes or astrocytes [27]. However, our recent work has shown that FEZ1 expression measured by microarray analysis was differentially expressed in two types of in vitro neonatal

astrocytes and has demonstrated that in astrocytes, FEZ1 protein levels were not lower than FEZ1 levels in neurones [28]. Despite its restricted expression

in the brain, new and intriguing roles for FEZ1 are continually revealed, as recent evidence implicates astrocytic FEZ1 expression in mood stabilization [29]. Furthermore, other evidence shows that FEZ1 may regulate dopaminergic neurone differentiation and dopamine release [30-32]. Collectively, these lines of evidence suggest a role for FEZ1 in PD. In this study, 6-Hydroxydopamine Hydrobromide (6-OHDA) was unilaterally injected in the medial forebrain bundle (MFB) of rats to induce the progressive pathological processes that model PD, as 6-OHDA selectively kills dopaminergic neurones. Next, FEZ1 expression was evaluated https://www.selleckchem.com/products/carfilzomib-pr-171.html in rat striatum and substantia nigra after 6-OHDA injection by real-time polymerase chain reaction (PCR) and Western blot analysis. FEZ1 localization in neuronal

or glial populations was examined by immunohistochemistry. Adult Sprague–Dawley (SD) male rats weighing 220–250 g (Experimental Animal Center of Soochow University, Suzhou, China) were used in all experiments. Animals were allowed to acclimate for 1 week and were Demeclocycline housed in a temperature-controlled colony room under a 12:12-h light–dark cycle with free access to food and water. Seventy rats were used: 58 were subjected to a 6-OHDA injection, and 12 were subjected to a sham operation. The experimental procedures were approved by Soochow University for ethics of experiments on animals. Male SD rats were anaesthetized with Chloral hydrate (400 mg/kg, intraperitoneally). After anaesthesia, the animals were placed in a stereotaxic apparatus (Stoelting, Wisconsin, WI, USA). 6-OHDA (10 μg of 6-OHDA hydrochloride in 5 μl of 0.02% ascorbic acid saline solution) was unilaterally injected in the MFB with a Hamilton syringe (0.46 mm in diameter) at a rate of 0.5 μl/min, and the needle was left in the place for 5 min after the injection. MFB injections of 5 μg of 6-OHDA per injection site were made at two injection sites relative to bregma, according to the rat brain atlas of Paxinos and Watson: AP, −1.8 mm; ML, −2.5 mm; DV, −8.0 mm, and AP, −1.8 mm; ML, −2.5 mm; DV, −7.5 mm [33].

Among the heterophilic antibodies, IgM RF was associated most closely with interference in the measurement of tryptase (P < 0·0001). We have not assessed the potential interference associated with IgG and IgA RF activity, which may be important. HAMA detected without RF rarely learn more caused interference. Interpretation of laboratory results should always be made in light of the clinical features. Test results are almost worthless without context. We recommend checking IgM RF levels and consider HBT treatment in all specimens where there is doubt about the significance of the MCT result. This may avoid unnecessary invasive investigations for mastocytosis

or inappropriate diagnosis of anaphylaxis. In anaphylaxis, this step may not be necessary provided that there are consecutive samples showing appropriate rise and fall of MCT values in an acute release pattern which cannot be mimicked by stable heterophile buy OSI-906 activity. The positive predicted value (PPV) of a rise and fall of tryptase in the context of an acute allergic reaction will not change, because the pretest probability is high and heterophilic interference is unlikely to change within 24 h. In this study cohort there were 24 raised MCT samples from anaphylaxis, which remained

elevated post-HBT treatment. However, the PPV of a persistently raised MCT > 20 µg/l as a screen for mastocytosis is likely to be impaired significantly. The positive predictive value of raised MCT alone is not as high as generally assumed when used as a surrogate screen for underlying mastocytosis or acute allergic reactions. Tryptase measurement must be interpreted in the clinical context Raised MCT values may be due to heterophile interference from RF rather than mast cell degranulation. All samples with unexplained or incongruous raised MCT values should be re-tested after treatment with heterophile blocking tubes. None. None. “
“Rheumatoid arthritis (RA) is a polyarticular inflammatory, angiogenic disease. Synovial angiogenesis contributes

to inflammation in RA. In Etofibrate this study we have developed an arthritic model in rats using a novel angiogenic protein (NAP), isolated from human synovial fluid of RA patients. We produced anti-NAP monoclonal antibodies (mAbs) and investigated the therapeutic efficacy of the same in adjuvant-induced or NAP-induced arthritis as a model of human RA. The treatment of arthritic rats with anti-NAP mAbs resulted in effective amelioration of paw oedema, radiological arthritic characteristics, serum levels of vascular endothelial growth factor (VEGF) and NAP, compared to that of untreated arthritic animals. Further, profiling of angiogenic markers such as synovial microvessel density, angiogenesis, CD31, VEGF and fms-like tyrosine kinase (Flt1) by immunohistochemistry both in arthritic and anti-NAP mAb-treated animals revealed the efficacy of mAb as an anti-angiogenic functional antibody.

27; 95% CI 0.06–1.15, P = 0.066, chi-squared test). However, there was no significant relation between the degree of eGFR improvement and delay in starting steroids (Pearson 3-Methyladenine ic50 r = −0.25, P > 0.45), and no difference in eGFR at the time of last follow-up (StG: 33 ± 3; SnG: 32 ± 7; P > 0.9, unpaired t-test). Conclusion:  StG patients had a greater degree of improvement in renal function, but with no correlation between degree

of improvement in eGFR and delay in starting steroids, and similar eGFR values at final follow-up. PPI were the second commonest drug category among drug-induced cases. “
“The current study was designed to observe the ultrastructural changes of podocyte foot processes during the remission phase and its relationship with the amount of the proteinuria in patients with minimal change disease (MCD). Electron micrographs of glomerular capillaries were taken from 33 adult cases with MCD, including 12 cases with nephrotic syndrome, 15 cases in partial remission and six cases in complete remission. The foot processes were classified into three grades by the ratio of the height to basal width: 0.5–1, 1–2 and ≥2. The foot process width (FPW) and the number

of foot processes in different grades per 10 μm of glomerular basement membrane (GBM) were measured. Normal renal tissues from 12 nephrectomies for Talazoparib in vitro renal carcinoma were selected as controls. There were statistical differences (P = 0.001) in the mean FPW among the nephrotic group (1566.4 ± 429.4 nm), partial remission group

(1007.8 ± 234.9 nm), complete remission group (949.8 ± 168.2 nm) and normal controls (471.9 ± 51.8 nm). For the height-to-width ratio ≥2, the number of foot process per 10 μm GBM was significantly greater in the normal group than that in the complete remission group (0.84 ± 0.24 vs. 3.84 ± 1.80, P = 0.016). Taking all three groups of patients together, the mean FPW showed correlation with the level of proteinuria (r = 0.506, P = 0.003). There may be no causal relationship between proteinuria and foot process effacement. In complete remission phase, both FPW and shape of foot process had not returned to normal while proteinuria disappeared. “
“The Chronic Kidney Disease Collaboration – Epidemiology (CKD-EPI) glomerular filtration rates (GFR) estimation Phosphoprotein phosphatase equation is believed to estimate GFR more accurately in healthy people but this has not been validated in Asians. We studied the distribution of GFR in a multi-ethnic Asian population without CKD, and compared the performance of measures of GFR estimation, including the CKD-EPI equation, Cockroft-Gault equation, and 24-hour urine creatinine clearances. A total of 103 healthy volunteers without a history of kidney disease, hypertension, or diabetes underwent GFR measurement using 3-sample plasma clearance of 99mTc-DTPA. Cockroft-Gault estimated GFR and 24-hour urine creatinine clearances were normalized to body surface area.

5°C with the majority of studies using 35°C or 35.5°C. In the BTM group patients underwent programmed cooling or isothermic dialysis, the temperature in the intervention group that underwent programmed cooling varied between 35.3°C and 35.7°C. The stability of the patients during HD also varied with BMS-777607 molecular weight a mixture of stable and unstable patients studied. A total of eight studies addressed the issue of IDH and cool temperature dialysis either using a fixed temperature reduction (6) or BTM (2).45,53–57

The overall rate of IDH was 7.1 times greater than in conventional dialysis (95% CI, 6.7–12.4) compared with thermo-regulated HD. In studies examining fixed temperature reduction the rate of IDH was 9.5 times less compared with the control while for those studies comparing isothermic cooling or programmed cooling the rate was 2 times less. When the data were adjusted for studies that had no IDH in the intervention group,45,56 the overall rate of IDH in cool dialysis was 2.6 times less compared with conventional dialysis (95% CI, 1.5–3.8). There was also a benefit on blood pressure post dialysis, with the higher values observed in cool dialysis, attributed to increased total peripheral

resistance. There were no differences in symptoms as reported find more by the patients. The issue of the optimal magnitude of temperature decrease was addressed in a recent trial (not included in the systematic review).58 Fourteen patients with a history of IDH were studied in a cross-over randomized trial. Isothermic dialysis was compared with ‘cooling’ dialysis (decrease core temperature by 0.5°C), with thermoneutral dialysis used as the control. The nadir of systolic blood pressure (SBP) during isothermic and thermoneutral dialysis was lower than during ‘cooling dialysis’ suggesting that greater stability is conferred by a small decrease in core body temperature. Temperature control can improve blood pressure stability in a IDH-prone population without causing discomfort or morbidity. The procedure is simple, safe and efficient to use. The Liothyronine Sodium early concerns regarding dialysis quality

have not materialized; however, long-term prospective validation is lacking. The precise temperature at which the benefit is derived needs to be balanced with symptoms of hypothermia. It is also likely that individual patients have a different temperature threshold at which a benefit to haemodynamic stability is conferred. More studies using the BTM devices are needed to further establish its role, especially in the adjustment of core body temperature based on the individual patient susceptibility to IDH. This would ideally occur in the form a randomized trial comparing fixed temperature reduction, isothermic dialysis and dialysis with a small decrease in core body temperature. Future studies of temperature controlled dialysis need to show a reduction in morbidity and mortality as well as a cost benefit in reducing hospitalization rates.

Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/our-partners.php. “
“Major histocompatibility complex (MHC) class II molecules present antigenic peptides derived from engulfed exogenous proteins to CD4+ T cells. Exogenous antigens are processed in mature endosomes and lysosomes where acidic proteases reside and peptide-binding to class II alleles is favoured. Hence, maintenance of the microenvironment within these organelles is probably central to efficient MHC class II-mediated antigen presentation. Lysosome-associated Selleckchem Bortezomib membrane

proteins such as LAMP-2 reside in mature endosomes click here and lysosomes, yet their role in exogenous antigen presentation

pathways remains untested. In this study, human B cells lacking LAMP-2 were examined for changes in MHC class II-restricted antigen presentation. MHC class II presentation of exogenous antigen and peptides to CD4+ T cells was impaired in the LAMP-2-deficient B cells. Peptide-binding to MHC class II on LAMP-2-deficient B cells was reduced at physiological pH compared with wild-type cells. However, peptide-binding and class II-restricted antigen presentation were restored by incubation of LAMP-2-negative B cells at acidic pH, suggesting that efficient loading of exogenous epitopes by MHC class II molecules is dependent upon LAMP-2 expression in B cells. Interestingly, class II presentation of an epitope derived from an endogenous transmembrane protein was Dolichyl-phosphate-mannose-protein mannosyltransferase detected using LAMP-2-deficient B cells. Consequently, LAMP-2 may control the repertoire of peptides displayed by MHC class II molecules on B cells and influence the balance between endogenous and exogenous antigen presentation. Major histocompatibility complex (MHC) class II molecules

present antigenic peptides derived from exogenous proteins to CD4+ T cells.1 These MHC class II proteins are constitutively expressed on the surface of a number of professional antigen-presenting cells (APC) such as dendritic cells, B cells and macrophages. The MHC class II complexes consist of α and β subunits which are first assembled in the endoplasmic reticulum with the chaperone molecule invariant chain (Ii).2,3 The cytoplasmic tail of Ii contains a motif that targets the Ii–MHC class II complexes to endosomal/lysosomal compartments. Here, acidic proteases degrade Ii to a small fragment known as class II-associated invariant chain peptide (CLIP), which remains associated with the MHC class II peptide-binding groove.4,5 Antigens delivered into the endosomal/lysosomal network via receptor-mediated or fluid-phase endocytosis are also exposed to proteases and denaturing reactions, yielding peptide ligands for class II molecules.