These previous studies in BALB/c mice suggested that the initial constraints regulating CDR-H3 content reflected germline sequence content; i.e. the product of natural selection. Superimposed upon these germline restrictions in diversity

were a series of somatic, presumably this website clonal, selective events that sequentially produced a CDR-H3 repertoire that had undergone “trimming” of apparently “disfavored” sequence content. This process included a reduction in the use of a specific VH gene segment, VH81X; a reduction in the use of very short CDR-H3s; enhanced use of reading frame 1; enhanced use of tyrosine and glycine in the CDR-H3 loop; and a sequential elimination of highly charged or heavily hydrophobic CDR-H3s with development. The present analysis of immunoglobulin repertoire development in the bone marrow of C57BL/6 mice again demonstrates the effects of germline-imposed restrictions on the range of initial diversity in the H-chain repertoire; but would point to significant differences in either the efficiency, the ability, or the direction of the late-stage somatic, clonal selective events in the bone marrow and the periphery. The end result is a mature, recirculating B-cell repertoire characterized by including IgM BCRs that bear antigen-binding sites that seemed to be not just “disfavored”,

but commonly “discarded” by the mature, recirculating BIBW2992 solubility dmso B cells in BALB/c mice. At the progenitor B-cell stage, the influence of the germline on the C57BL/6 repertoire is obvious. VH, DH, and JH usage in C57BL/6 H-chain transcripts appears to differ from BALB/c H-chain transcripts both due to changes in number as well as the sequence of homologous gene segments. Germline variation appeared to be associated with changes in VDJ rearrangement frequency, although this latter point needs to be confirmed through the analysis of nonfunctional sequences. Among the features

of the C57BL/6 repertoire that most closely matched the BALB/c repertoire were similarities in the initial distribution Benzatropine of N addition, lengths, charge, and the usage of 18 of the 20 different potential amino acids. One of the features that varied between the two strains reflected the diminished number of functional VH gene segments, including the absence of the most commonly used VH in the BALB/c genome, VH7183.10. Others included the enhanced use of serine-enriched DFL16.1; the presence of a DSP2.11 homologue, DSP2.x, that encodes serine in RF1; and an increased use of JH1 in place of JH4. Of these changes, the most apparent effect in early B-cell progenitors was on VH content, again due to the absence of many of the VH7183 variant sequences available to BALB/c mice.

A role for SEMA3A in termination of DC/T-cell interactions by repulsive destabilization of the conjugates on NP-1 interaction has been proposed 34, and in line with this, SEMA3A was produced only late after onset of allogeneic MLRs (34 and Fig. 4B). In contrast, SEMA3A production from MV-DC alone or in co-cultures with allogeneic T cells raised within few hours, indicating that this might contribute to destabilization of the IS as described to occur in these cultures earlier 10 and as evidenced by lower frequencies of stable conjugates on exogenous addition of SEMA3A (and also SEMA6A)(Fig.

6B). Notably, amounts of SEMA3A released from MV-DC/T-cell co-cultures several fold exceeded those determined to actively inhibit T-cell Selleck PCI32765 expansion stimulated allogeneic Fostamatinib concentration LPS-DC 34 or on αCD3/CD28 ligation 36. In line with previous reports 38, 39, we repeatedly detected especially in the co-cultures, at least two SEMA3A species (Fig. 4B), the generation of may involve intracellular or surface proteolytic processing, e.g. furin or membrane-resident metalloproteases 48. Whether production of two species in the MV-DC/T-cell cocultures relates to higher infection levels (as compared to the MV-DC only, Fig. 4A) or to the presence of allogeneic T cells remains to be resolved.

While abrogation of NP-1/SEMA3A interaction reportedly signficantly improved allogeneic T-cell expansion driven by LPS-DC 34, this and conjugate stability in MV-DC/T-cell co-cultures could not detectably be rescued by SEMA-neutralizing

antibodies (not shown). This is, however, not surprising since the presence of the MV gp complex on the DC surface within the DC/T-cell interface has previously been linked to IS destabilization and contact-mediated inhibition of T-cell expansion 10, 47, 49, 50. It is also because MV particles Sinomenine displaying the inhibitory complex were likely present in conditioned supernatants of MV-DC or MV-DC/T-cell co-cultures containing high levels of SEMA3A that we did not directly prove their activity on αCD3/CD28-stimulated T-cell expansion. In contrast to earlier studies 34, 36, SEMA6A was at least as efficient at interferring with IS stability and function as SEMA3A (Fig. 6B). As the IgG control always included at comparable levels did not have any effect on all parameters determined except for T-cell motility (Fig. 6A), and ligation of murine plexA4 by SEMA6A is known to negatively regulate T-cell responses 51, we consider the activity of SEMA6A in the assay as specific and thus, the obvious discrepancy cannot be explained at present, and needs further experimentation which would, as the identification of the cellular source of SEMA6A, exceed the present study.

We compared fluorescence in CD56bright CD16− versus CD56dim CD16+ NK cells and observed a higher fluorescence in this latter subpopulation (Fig. 6D). Moreover, using a co-immunoprecipitation assay, we observed a direct interaction between CD16 and VLPs

since we detected the presence of L1 from VLPs only when viral particles and CD16 were immunoprecipitated with anti-CD16 antibody (Fig. 6E). We used normal mice IgG and an antibody against an unrelated protein (EGF receptor, EGFR) as negative controls. Finally, we confirmed the role of CD16 by blocking the LYNX-VLP binding and internalization with a pre-incubation of NK cells with blocking anti-CD16 mAb (Fig. 6E). Similarly, this mAb also inhibited VLP entry into NK92 click here CD16+ cells (data not shown). FITC-dextran uptake assays find more showed that VLP internalization is mediated by macropinocytosis in NK92 CD16+ cells (Fig. 6F) (viability of NK92 in the presence of drugs is shown in Supporting Information Fig. 3B). In contrast, the presence of VLPs did not change FITC-dextran uptake by NK92 CD16− cells (Supporting Information Fig. 6). In order to determine the role of CD16 in NK-cell function in the presence of VLPs, we compared the cytotoxic activity of CD16+ and CD16− NK92 cells. As opposed to NK92 CD16+ cells, NK92 CD16− cells were not able to degranulate in the presence of VLPs although

these cells increased their cytotoxic granule release in the presence of PMA/ionomycin which is the most common and potent stimulator of NK-cell cytotoxic function (Fig. 7A). Similarly, VLPs induced an increased killing of CasKi cells by NK92 CD16+ cells (Fig. 7B) but not by NK92 CD16− cells (Fig. 7C). We also observed higher cytokine production, both of IFN-γ (Fig. 7D) and TNF-α (Fig. 7E), in the presence of VLPs only in NK92 CD16+ nearly culture supernatant. Understanding the interactions between HPVs and immune cells is important in order to dissect the mechanisms responsible for the viral clearance observed in the majority of patients with SIL 8. Moreover, the immune response against HPV induced by HPV–VLP vaccination is poorly characterized. In this

study, we demonstrated that NK cells recognize, internalize and respond to VLPs by cytotoxic granule exocytosis and cytokine production. In cervical tissue samples, we observed that NK cells infiltrate mainly HPV-associated preneoplastic lesions where HPV particles are produced, but less SCC where the expression of L1 protein is not detected 19. These findings confirm previous data using a less specific marker for NK cells, CD56, and showing an increased number of CD56+ cells in HPV-related preneoplastic lesions 29, 30. Moreover, NK cells may also interact with VLPs used as a prophylactic anti-HPV vaccine 6, since the adjuvant present in the vaccine induces local inflammation 31, and since infiltration of NK cells has been observed in inflamed tissues 32.

In-vitro differentiative potential of MSCs is not restricted

to mesodermal lineages, but their transdifferentiation into other lineages, such as endothelia, could be realized PS-341 order both in vitro and in vivo [5]. In addition, MSCs exhibit immunoregulatory activities, inhibiting the function of different immune cells of innate and adaptive immunity [6], blocking the division of stimulated T cells, preventing irreversible G0/G1 phase arrest and stopping T cell division in mixed lymphocyte reactions (MLRs) [7]. However, the immunomodulatory activity of the MSCs does not rely solely upon T cells, but also upon the first step of the immune response through the inhibition of dendritic cell differentiation and maturation in antigen-presenting cells [8]. Furthermore, their regulatory activity may be amplified by modulating immune responses via the de-novo induction and expansion of CD4+CD25+forkhead box protein 3 (FoxP3)+ regulatory T cells (Tregs). Tregs play a critical role in peripheral self-tolerance, as well as in the regulation of acquired immunity, by inhibition of lymphocyte proliferation [9, 10]. As well as Tregs developing in the

thymus (natural Tregs), a Treg population can be induced from peripheral naive selleck chemicals llc T cell (inducible Tregs), and these inducible Tregs can be recruited directly by MSC from CD4+ T cells [11, 12]. In recent decades many studies have been published addressing the role of Treg number and function in human autoimmunity [13], suggesting that their possible defective function plays a role in many autoimmune diseases. On this basis, both the regenerative and the immunomodulatory properties of MSCs make them an attractive candidate 3-oxoacyl-(acyl-carrier-protein) reductase for cellular therapy in autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease in which alteration of cellular immunity, including T and B lymphocytes, has been largely

studied both in the skin and in internal organs [14, 15]. Furthermore, recent evidence has shown an aberrant dendritic cell function in SSc, contributing to the molecular milieu of the disease [16]. We have shown previously that MSCs obtained from SSc patients (SSc–MSC) were normal with respect to clonogenicity and differentiative capacity, although they displayed early senescence and were defective in acquiring some differentiative functions [17]. Senescent MSC generally show a flattened morphology, over-expression of senescence-associated β-galactosidase (β-Gal) activity, reduced telomerase activity and increased expression of both p53 and p21, which are negative regulators of cell proliferation [18]. At present, only few papers have investigated the immunoregulatory activity in SSc.

WZW is the corresponding author. All authors read and approved the final manuscript. The authors declare that they have no competing interests. “
“Although periodontal tissue is continually challenged by microbial plaque, it is generally maintained in a healthy state. To understand the basis for this, we

investigated innate antiviral immunity in human periodontal tissue. The expression of mRNA encoding different antiviral proteins, myxovirus resistance A (MxA), protein kinase R (PKR), oligoadenylate synthetase see more (OAS), and secretory leukocyte protease inhibitor (SLPI) were detected in both healthy tissue and that with periodontitis. Immunostaining data consistently showed higher MxA protein expression in the epithelial layer of healthy gingiva as compared with tissue with periodontitis. Human MxA is thought to be induced by type I and III interferons (IFNs) but neither cytokine type was detected in healthy periodontal tissues. Treatment in vitro of primary human gingival epithelial cells (HGECs) with α-defensins, but not with the antimicrobial peptides β-defensins or LL-37, led to MxA protein expression. α-defensin was also detected in healthy periodontal tissue. In addition, MxA in α-defensin-treated HGECs was associated with protection against avian influenza H5N1 infection and silencing of the MxA gene using MxA-targeted-siRNA abolished this antiviral activity. To our knowledge, this is the first study to uncover

a novel pathway of human MxA the induction, which is initiated by an endogenous antimicrobial peptide, namely α-defensin. This pathway may play an important role in the first line of antiviral Silmitasertib chemical structure defense in periodontal tissue. Periodontal tissue is a tooth-supporting structure, which includes gingiva, periodontal ligaments, cementum, and alveolar bone. Chronic inflammation of the periodontal tissue, periodontal disease, is one of the most common inflammatory diseases in humans. The advanced form of the disease, periodontitis, with severe bone destruction may cause tooth loss. The etiologic importance

of bacteria in periodontal disease has been well recognized. Bacterial plaque biofilms continually form on the tooth surfaces adjacent to gingiva. Recent studies have proposed that viral co-infection could enhance the development and progression of periodontitis [[1, 2]]. Detection of herpes simplex virus (HSV) types 1 and 2, human cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV), have been reported in dental plaque biofilm, gingival crevicular fluid, and periodontitis tissue specimens [[3]]. In healthy periodontal specimens, some viral deoxyribonucleic acid (DNA) can also be found, but generally at lower levels than in periodontitis [[4-6]]. Even so, the precise role of viruses in periodontal disease remains unclear. Periodontal tissue is continually exposed to bacterial plaque; therefore an effective innate immune response is critical to maintain homeostasis.

Pathological examination revealed that the resection edge of the extradural component consisted of a spinal nerve with thickened epineurium and was free of neoplastic cells. No schwannoma component was evident in the intradural tumor. No obvious transition thus existed between the extra- and intradural tumors. Distinguishing these tumors prior to surgery is critical for determining

an optimal surgical plan, as schwannoma and meningioma require different surgical procedures. We therefore recommend a careful review of preoperative imaging with the possibility of concurrent tumors in mind. “
“M. Paradisi, M. Fernández, G. Del Vecchio, G. Lizzo, G. Marucci, M. Giulioni, selleck compound E. Pozzati, T. Antonelli, G. Lanzoni, G. P. Bagnara, Roxadustat in vivo L. Giardino and L. Calzà

(2010) Neuropathology and Applied Neurobiology36, 535–550 Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy Aims: Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero-mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. Methods: Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence Methisazone of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT-PCR in neurospheres. Results: We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration.

Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor). Conclusion: We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS. “
“A polymorphous variant of oligodendroglioma was described by K.J. Zülch half a century ago, and is only very sporadically referred to in the subsequent literature. In particular, no comprehensive analysis with respect to clinical or genetic features of these tumors is available.

OCT offered the second best sensitivity but displayed the lowest specificity. CLSM and KOH preparation showed a high specificity and CLSM offered the best positive predictive value, similar to KOH preparation and OCT. Fungal culture showed the lowest sensitivity and the worst negative predictive value, yet culture and PCR are the only techniques able to identify genus and species. In summary, CLSM was comparable to PAS staining and superior to KOH preparation. Due to the low specificity we assess OCT not as appropriate. In the differentiation of species PCR outplays the fungal culture in terms of

time and sensitivity. “
“Candida africana is a recently described opportunistic yeast pathogen that has been linked to vaginal candidiasis. This yeast was first described, in 1995, as atypical chlamydospore-negative Candida PLX3397 order albicans strain,

and subsequently proposed as a new Candida species on the basis of morphological, biochemical and physiological characteristics clearly different from those of typical C. albicans isolates. Phylogenetic studies based on the comparison of ribosomal DNA sequences demonstrated that C. africana and C. albicans isolates are too closely related to draw any conclusions regarding the status of a new species. Therefore, on the basis of these studies, some authors considered C. africana as a biovar of C. albicans even if genetic differences may be found if additional regions of genomic DNA are sequenced. fantofarone The taxonomic situation of C. Ixazomib manufacturer africana and its phylogenetic relationship with other Candida species is still controversial and remains, at present, a matter of debate. Our goal is to review the current knowledge about C. africana and highlight the development of rapid and accurate tests for its discrimination from C. albicans, Candida dubliniensis and Candida stellatoidea. Furthermore, through the analysis of literature data, we have found that C. africana has a worldwide distribution and a considerable number of features making its study particularly interesting. “
“Invasive fungal infections cause significant morbidity and mortality

in immunocompromised patients. Azoles, and fluconazole in particular, are very active against Candida albicans, and are used widely because of their good tolerability. However, the increasing use of azole antifungals for the treatment of mucosal and systemic Candida infections has resulted in the selection and/or emergence of resistant Candida strains. The main mechanisms of azole resistance among Candida species are the development of bypass pathways, alterations in the ERG 11 gene encoding the azole target enzyme, and the up-regulation of genes encoding efflux pumps. A better understanding of the mechanisms and clinical impact of antifungal resistance is essential to prompt and efficient treatment of patients with invasive mycoses and to improve the outcome of such infections.

Pregnancies with medical complications or diseases were excluded. The placental villi tissues were collected during the suction curettage procedure. The placental villi from first-trimester pregnancies were carefully dissected

free of attached placental selleck products or myometrial tissue as well as visible blood clots and then washed twice in 0.9% NaCl as soon as the embryonic tissues were removed from the uterus. Samples were stored at −80°C and later processed to extract tissue protein. Biopsies were taken from the placental villi, and small blocks of tissue were obtained by cutting longitudinal sections of 3–5 mm maximum thickness. The blocks were immersed immediately for 2 hr in phosphate-buffered 2.5% gluteraldehyde. After overnight washing in a 0.1 m sodium phosphate buffer, the tissue blocks were post-fixed in 1% OsO4 in a 0.1 m phosphate buffer (pH 7.4) for 1 hr and stained with 1% uranyl acetate. Afterwards, the tissue blocks were dehydrated and flat-embedded in Durcupan (Fluka Chemic AG, Sweden). For electron microscopy (EM), ultrathin sections (60–70 nm) were stained with lead citrate, examined at 3700× and selleck 12500× magnification and photographed using a Zeiss 109 electron microscope (Carl Zeiss, Oberkochen, Germany). HTR-8/SVneo and HPT-8 cells were grown in Dulbecco’s modified Eagle’s medium/Ham’s F-12 medium supplemented

with 1% non-essential amino acids, 2 mm glutamine and 10% heat-inactivated foetal bovine serum in a 37°C incubator with 5% CO2. Complementary DNA (cDNA) to gC1qR was constructed in-frame using the BamHI/EcoRI sites of the pcDNA 3.1 vector. The resulting

gC1qR vector was then transfected into HTR-8/SVneo and HPT-8 cells according to the vendor’s protocol. Briefly, 500 pmol of gC1qR vector and 10 μL of Lipofectamine 2000 were diluted in 750 μL of OptiMEM (Life Technologies). After pre-incubation for 45 min at 37°C, the solutions were mixed and incubated for an additional 15 min at room temperature. The Lipofectamine 2000/gC1qR vector mixture was subsequently overlaid onto the cells and incubated for 2 hr. Finally, 1 mL of growth medium (20% FCS) per well was added for further cultivation of the cells. Reporter gene activities were normalized to total protein levels, and all of the results represent the average of triplicate experiments. We designed an siRNA to target the 408–426 nucleotide portion of human gC1qR mRNA; the forward sequence Liothyronine Sodium was 5′-AAC AAC AGC AUC CCA CCA ACA UU-3′. Using pGenesil-1 as the vector backbone, a gC1qR siRNA-expressing plasmid was constructed. Near the 5′ end of the two oligonucleotides were BamHI and HindIII restriction site overhangs; a 6-nucleotide poly-T tract recognized as an RNA pol III termination signal was located at the 3′ end of the siRNA template. The siRNA was synthesized, annealed and ligated into the BamHI and HindIII restriction sites of the pGenesil-1 expression vector. A vector containing siRNA for an unrelated gene was used as a negative control.

In the past decade, KPD has become the fastest growing source of transplantable live donor kidneys, overcoming the barrier faced by LD deemed incompatible Enzalutamide cost with their intended recipients.[8] Reasons for participating in KPD include primarily blood group incompatibility and sensitization of the recipient against the donor, but may additionally include the potential for improvement in transplant quality and tissue compatibility. In the absence of a well-organized DDKTx program, or when transplantation

with HLA-desensitization protocols and ABO incompatible transplantation is either unaffordable or poses a greater risk due to more intensive immunosuppression, KPD promises hope to a growing number of ESKD patients.[9-11] Of all the advances made in KTx in the last 25 years, KPD has the greatest potential to expand the LD pool. However, KPD is still in its infancy and needs further development. Ethical, administrative, and logistical barriers initially proved formidable and prevent the implementation of KPD programs. Lack of awareness, counselling and participation are other important issues. Although KPD was underutilized in India, recently, KPD transplantation has been performed Sotrastaurin cell line more frequently.[9-19] KPD is feasible for any centre that performs LDKTx. However, we do not have a National KPD program and one of the limitations of a single centre

KPD program is that the donor pool is small. A national KPD program will substantially increase the donor pool, but there are some barriers that need to be overcome to enable establishing a successful national program (Table 2). Nevertheless,

recent studies are valuable for encouraging the participation of KPD pairs and transplant centres in the national KPD program. Issues regarding legal permission in our country Concerns regarding the donor-recipient age difference affecting the allograft outcome. Is there any difference in graft survival between KPD versus living donor kidney transplantation (LDKTx)? Whether increased cold ischemia Fluorometholone Acetate time (CIT) would affect the allograft outcomes? Waiting time for deceased donor versus KPD transplantation/LDKTx. Should KPD be performed for better human leukocyte antigen (HLA) matching? In developing countries such as India, extending KPD to HLA-mismatched, albeit compatible patient-donor pairs would increase well-matched LDKTx, resulting in use of less immunosuppression and fewer expenses, lower infective morbidity, and better survival. A model for KPD based on HLA matching is presented. They have shown that 40% of prospective recipients without well-matched donors would find a donor-swap pair based on HLA matching within a year, with coordination among four national centres and a shared HLA registry.[15] We have performed a total of 160 KPD KTx at our single centre from 2000 to 2014.

Therefore, we carried out supernatant transfer experiments under conditions in which the synthetic TLR-2 agonist was washed from cells prior to supernatant conditioning. Supernatants conditioned for 6 h were sufficient to induce CD1a expression on fresh monocytes (Fig. 3C), although the percentage of cells expressing CD1 was lower than the percentage of CD1-positive cells treated directly with the TLR agonists. This decrement is expected because HTS assay factors may be consumed during conditioning and were diluted during transfer. Thus, TLR-2 agonists work

via mechanism that requires only minutes of TLR stimulation but plays out over 3 days in a process that involves cell to cell transfer of

host factors. To identify the host factors, we first screened conditioned supernatants using a multiplex bead-based cytokine array. Consistent with known patterns of TLR-2 dependent cytokine secretion 26, 41, we detected increased levels of IL-1β, IL-6, IL-8 and TNF-α, Selleck PR 171 and we also found GM-CSF in monocyte supernatants. Using recombinant cytokines, we found that GM-CSF or IL-1β were sufficient to induce CD1a, CD1b and CD1c expression (Fig. 4A,C and data not shown). Quantitative ELISA detection showed that both GM-CSF and IL-1β were detected in conditioned supernatants within the dose range at which recombinant cytokines activate CD1a expression (∼100–500 pg/mL), consistent with the conclusion that both contribute to CD1 induction (Fig. 4A–C, Supporting Information Fig. S1 and data not shown). The role of GM-CSF in CD1 induction has been previously observed with recombinant cytokines 12 or mycobacterial infection 17, so we considered this a confirmatory result, while extending the range of pathogens that work via this mechanism. We undertook more detailed studies of IL-1β because it is

a key mediator of innate immunity that occurs downstream of TLRs, potentially providing insight in the pathways that connect TLR ligation to CD1 induction. Also, the potential role of IL-1β in CD1 gene regulation was not previously known and therefore represented a new adjuvant for activating the CD1 system. In our study, the CD1a induction was seen in response to two preparations of recombinant mature IL-1β (17Kd) that were free of detectable PtdIns(3,4)P2 lipopolysaccharide (data not shown). Also, anti-IL-1β blocked CD1a induction, demonstrating that IL-1β was the only active component in the recombinant cytokine preparation (Supporting Information Fig. S1). Measurement of surface expression of all three group 1 was upregulated from trace to high levels in a dose-dependent fashion by IL-1β (Fig. 4C), whereas the group 2 CD1 protein (CD1d) was unaffected (Fig. 4C). Further, IL-1β induction of group 1 proteins increased activation of CD1a autoreactive T cells (Supporting Information Fig. S2).