Three dimensional structure directs T-cell epitope dominance associated with allergy

<p>Abstract</p> <p>Background</p> <p>CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens.</p> <p>Methods</p> <p>The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy.</p> <p>Results</p> <p>Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen.</p> <p>Conclusion</p> <p>During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.</p

Osteoclast Activated FoxP3+ CD8+ T-Cells Suppress Bone Resorption in vitro

BACKGROUND: Osteoclasts are the body's sole bone resorbing cells. Cytokines produced by pro-inflammatory effector T-cells (T(EFF)) increase bone resorption by osteoclasts. Prolonged exposure to the T(EFF) produced cytokines leads to bone erosion diseases such as osteoporosis and rheumatoid arthritis. The crosstalk between T-cells and osteoclasts has been termed osteoimmunology. We have previously shown that under non-inflammatory conditions, murine osteoclasts can recruit naïve CD8 T-cells and activate these T-cells to induce CD25 and FoxP3 (Tc(REG)). The activation of CD8 T-cells by osteoclasts also induced the cytokines IL-2, IL-6, IL-10 and IFN-γ. Individually, these cytokines can activate or suppress osteoclast resorption. PRINCIPAL FINDINGS: To determine the net effect of Tc(REG) on osteoclast activity we used a number of in vitro assays. We found that Tc(REG) can potently and directly suppress bone resorption by osteoclasts. Tc(REG) could suppress osteoclast differentiation and resorption by mature osteoclasts, but did not affect their survival. Additionally, we showed that Tc(REG) suppress cytoskeletal reorganization in mature osteoclasts. Whereas induction of Tc(REG) by osteoclasts is antigen-dependent, suppression of osteoclasts by Tc(REG) does not require antigen or re-stimulation. We demonstrated that antibody blockade of IL-6, IL-10 or IFN-γ relieved suppression. The suppression did not require direct contact between the Tc(REG) and osteoclasts. SIGNIFICANCE: We have determined that osteoclast-induced Tc(REG) can suppress osteoclast activity, forming a negative feedback system. As the CD8 T-cells are activated in the absence of inflammatory signals, these observations suggest that this regulatory loop may play a role in regulating skeletal homeostasis. Our results provide the first documentation of suppression of osteoclast activity by CD8 regulatory T-cells and thus, extend the purview of osteoimmunology

Autoimmunity to type VII collagen in SKH1 mice is independent of regulatory T cells

SUMMARY: Epidermolysis bullosa acquisita is an autoimmune blistering disease characterized by circulating and skin basement membrane-bound IgG autoantibodies to type VII collagen, a major structural protein of the dermal–epidermal junction. Regulatory T cells (T(reg)) suppress self antigen-mediated autoimmune responses. To investigate the role of T(reg) in the the autoimmune response to type VII collagen in a mouse model, a monoclonal antibody against mouse CD25 was used to deplete T(reg). A recombinant mouse type VII collagen NC1 domain protein and mouse albumin were used as antigens. SKH1 mice were used as a testing host. Group 1 mice received NC1 immunization and were functionally depleted of T(reg); group 2 mice received NC1 immunization and rat isotype control; and group 3 mice received albumin immunization and were functionally depleted of T(reg). Results demonstrated that anti-NC1 IgG autoantibodies with high titres, as determined by enzyme-linked immunosorbent assay and Western blotting, developed in all mice immunized with NC1 (groups 1 and 2), but were undetected in group 3 mice. The predominant subclasses of anti-NC1 autoantibodies were IgG1, IgG2a and IgG2b; furthermore, these antibodies carried only the kappa light chain. IgG autoantibodies in the sera of NC1-immunized mice reacted with mouse skin basement membrane in vitro and deposited in skin basement membrane in vivo as detected by indirect and direct immunofluorescence microscopy, respectively. Our data suggest that the development of autoimmunity against type VII collagen in mice is independent of T(reg) function and the autoimmune response is mediated by both Th1 and Th2 cells. We speculate that the basement membrane deposition of IgG may eventually lead to blister development

Análise da expansão rápida da maxila por meio da tomografia computadorizada Cone-Beam Analysis of rapid maxillary expansion using Cone-Beam computed tomography

Diante do diagnóstico de uma arcada maxilar esqueleticamente atrésica, o tratamento de escolha geralmente é a expansão ortopédica da maxila, envolvendo a separação da sutura palatina mediana. A avaliação dessa sutura era basicamente realizada por meio da radiografia oclusal superior, limitando sua análise em norma frontal. Da mesma forma, quantificar essa atresia radiograficamente nas telerradiografias cefalométricas sempre foi um obstáculo para o clínico, devido à grande sobreposição das estruturas faciais. O advento da tomografia computadorizada na Odontologia tem transformado a forma de diagnóstico devido à alta precisão na avaliação das dimensões das estruturas faciais, possibilitando quantificar de maneira fiel o comportamento das hemimaxilas, a inclinação dentária, a formação óssea na sutura nos três planos do espaço, assim como a reabsorção óssea alveolar e demais consequências da expansão palatina<br>Whenever a maxillary arch is diagnosed as skeletally atresic the treatment of choice is usually maxillary orthopedic expansion, involving separation of the midpalatal suture. Basically, this suture used to be assessed with the aid of a maxillary occlusal radiograph, which limited its posteroanterior evaluation. Similarly, quantifying this atresia in cephalometric x-rays always posed an obstacle for clinicians owing to considerable superimposition of facial structures. With the advent of computed tomography, this technology has revolutionized diagnostic methods in dentistry because it provides high dimensional accuracy of the facial structures and a reliable method for quantifying the behavior of the maxillary halves, tooth inclination, bone formation at the suture in the three planes of space, as well as alveolar bone resorption and other consequences of palatal expansio