Frits Koning

..However, wheat gluten proteins cause celiac disease (CD) in 0.5 to 1% of the general population. Among these proteins, the alpha-gliadins contain several peptides that are associated to the disease...

..Once tolerance is broken, a broad gluten-reactive T cell repertoire may develop through determinant spreading. This may be a critical step toward full-blown disease...

..Moreover, I discuss whether it is feasible to alter wheat and/or gluten to make it suitable for consumption by CD patients...

..Thus, gluten molecules contain a large number of immunogenic peptides and this is likely to play an important role in the breaking of oral tolerance to gluten...

..They also may be of relevance for our understanding of other multifactorial disorders including IBD and HLA-associated autoimmune diseases...

..Together, these observations provide a unique explanation for the disease inducing capacity of gluten...

..Although long thought to be impossible, recent results suggest that the development of nontoxic wheat varieties may be feasible, which would aid disease prevention and provide an alternative food source for patients...

..Our findings provide a molecular basis for the association between HLA-DQ transdimers and T1D and set the stage for rational testing of potential diabetogenic peptide epitopes...

..This knowledge may be an important asset in the development of future treatment strategies...

..Because type 1 diabetes is strongly associated with the presence of HLA-DQ8trans, our findings may bear relevance to this disease as well...

..This threshold model might also help to understand the development of refractory celiac disease and lymphoma...

..Moreover, the results provide a first step toward a rational strategy for gluten detoxification via targeted mutagenesis at the genetic level...

..This knowledge may be of importance for the identification of additional T-cell stimulatory gluten peptides and the design of a peptide-based, tolerance-inducing therapy...

..Such immune-stimulatory peptides are found in both gliadins and glutenins. Monoclonal antibodies (mAbs) against these peptides can be used to screen food for the presence of such peptides...

..Such peptides are candidate lead peptides for further optimization. Our results, however, also indicate that in order to obtain further significant increases in binding affinity alternative approaches will have to be explored...

..The only cure for CD is a lifelong gluten-free diet. It is unknown, however, if all wheat varieties are equally harmful for patients. We investigated whether wheat varieties exist with a natural low number of T-cell-stimulatory epitopes...

..Together, these results indicate that HLA-DQ2 and HLA-DQ8 associate with an alternative CLIP sequence, a property that may relate to the strong association between HLA-DQ molecules and human autoimmune diseases...

..The aim of this study was to determine the correlation between HLA-DQ/DR-based genotypes and the variation in phenotypes of the disease...

..Hence, the KIR transgene mediated "missing self" recognition in vivo. We anticipate that this KIR and HLA transgenic mouse will help shed light on KIR and HLA effects in disease and transplantation...

..This study confirms previous work on epithelial lysis by RCD cell lines and identifies a novel mechanism that potentially contributes to the gluten-independent tissue damage in RCD II and RCD-associated lymphoma...

..6 to 45.9%. Both statistical parameters were in the acceptable range of ELISAs under these conditions, and the method will be presented to the Codex Alimentarius as a preferred method for gluten analysis...

..The possibility that deamidation drives the GLU response toward immunodominant T-cell stimulatory peptides after disease initiation is discussed...

..This model may have important implications for disease prevention...

..It also provides the information to design and introduce safe gluten genes in other cereals, which would exhibit improved quality while remaining safe for consumption by celiac disease patients...

..Our results suggest that M-PLP139-151 inhibits EAE development by affecting the differentiation of T cells into encephalitogenic effector cells...

..We aimed to determine the prevalence of unrecognized CD in subfertile male-female couples visiting a fertility clinic compared with the general population...

..niger efficiently degrades gluten proteins. Future studies are required to determine if the prolyl endoprotease can be used as an oral supplement to reduce gluten intake in patients...

..Pre)malignant transformation in RCD II thus correlates with defective synthesis or defective association of the TCR chains, resulting in loss of surface TCR-CD3 expression...

..Moreover, some of these peptides were found to be non-immunogenic and block gluten induced immune responses. These can thus serve as lead compounds for the development of HLA-DQ2 blocker peptides...

..Thus, the rapid evolution of activating KIR may have allowed for efficient NK-cell control of viruses, but may also have increased the risk that slowly evolving T-cell responses to persistent pathogens derail into autoimmunity...

..A number of patients, however, discontinue the gluten-free diet (GFD) without developing symptoms or signs. The aim of our study was to investigate whether CD patients are capable of developing tolerance to gluten...

..Our objective was to determine the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn's disease...

....

..Thus, the CMV-induced down-regulation of HLA class I may in fact enhance memory CMV-specific CD4(+) T cell responses restricted by HLA class II...

..This provides a rationale for the observation that celiac disease patients are intolerant to these cereal proteins but not to other common food proteins...

..In line with these findings, both transgene-encoded KIR and endogenous NKG2A contributed to the rejection of cells lacking HLA-Cw3. These findings support the idea that HLA influences the human KIR repertoire...

..The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis model and gain more insight into protective mechanisms...

..The enzymatic degradation of gluten might become an alternative to the gluten-free diet, and recent work indicates that such approaches are getting close to being tested in clinical trials...

..In this study, three novel lines of evidence were identified that support a role for NK cells...

..Therefore, mannosylated antigens may represent a novel therapeutic approach for antigen-specific modulation of autoreactive T cells in vivo...

..This explains why they act as immunogenic neoantigens. The newly discovered epitopes can be exploited for immune intervention against processing-deficient tumors through adoptive T-cell transfer or peptide vaccination...

..In approximately 40% of patients with RCDII these lymphocytes develop into an invasive lymphoma. In the current study we aimed to identify the physiological counterpart of these cells...

..Together, our data indicate that KIR-expressing CD4 T cells are predominantly HLA class II-restricted effector memory Th1 cells, and that a significant, previously unrecognized fraction of effector memory Th1 cells expresses KIR...

..The treatment is a strict gluten-free diet (GFD). The purpose of this study was to investigate whether the naturally gluten-free cereal Eragrostis tef (tef) is associated with health problems when used by CD patients...

..Since Abs that are only reactive with HLA loaded with irrelevant peptides are expected to be harmless toward allografts, the practice of HLA Ab determination on lymphocyte-derived HLA deserves reconsideration...

..Importantly, this correlated with an increase in filamentous actin and the appearance of veils, suggesting a role for cofilin in cytoskeletal rearrangements during maturation...

..Clinical follow-up of celiac disease patients eating oats is advisable...

..In conclusion, mannosylated peptide induces proliferation of T cells with impaired T(h)1 cell effector functions and additionally abrogates the activity of pre-existing effector T cells...

..Our data suggest that M-PLP(139-151) induces peptide-specific tolerance to EAE via a mechanism of deletion or impaired migration of encephalitogenic T cells...

..This is specially relevant to processes involving epithelial T cell interactions such as organ-specific autoimmunity and transplant rejection...

..Selective enrichment of CD1d-alphaGalCer-restricted NKT cells at the site of inflammation is observed in PBC, suggesting a role of these cells in the development of PBC...

..These are further supported by the activity determinations in which we observed no differences in PREP activity between CD patients and controls...

..However, unlike superantigens, Ni requires idiotypic, i.e., CDR3alpha-determined TCR amino acids. This new type of TCR-MHC linkage might explain the high frequency of Ni-reactive T cells in the human population...

..We also determined the enzymatic activity of PGPEPI in duodenal biopsies. Our results uniformly indicate that PGPEP1 is not involved in the aetiology and pathology of CD...

....