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C Mawas

Publications and source records attributed to C Mawas.

118 records · Page 7Linked to original sources
PubMedDate not supplied

Transmembrane signaling via both CD3 and CD2 human T cell surface molecules involves protein kinase-C translocation.

The activation of T lymphocytes by appropriate pairs of anti-CD2 monoclonal antibodies has been shown to involve phospholipase-C and phosphoinositide hydrolysis. In this paper we show that the stimulation of the human cloned leukemic T cell line Jurkat by anti-CD2 as well as anti-CD3 monoclonal antibodies induces translocation from cytosol to cell membrane of protein kinase-C (PKC), which is dependent on the formation of 1,2-diacylglycerol from inositol 4,5-diphosphate. PKC translocation is rapid and transient: the kinetics of enzyme redistribution are similar for CD2 and CD3. These results further stress that CD2 and CD3 T cell activation pathways use similar signal transducing mechanisms.

Antibodies, Monoclonal↗
PubMedDate not supplied

Dissociation between early and late events in T cell activation mediated through CD28 surface molecule.

The regulation of early and late events of T cell activation via the CD28 molecule has been investigated, using as an indicator system the differentiated leukemic T cell line Jurkat. Both CD3 and CD28 mAbs induced an increase in (Ca2+)i in Jurkat cells, although with different kinetics, the latter being slower than the former. CD28-mediated (Ca2+)i mobilization was highly sensitive to cholera toxin (ID50 25 ng/ml, vs 300 ng/ml for CD3 stimulation). The inhibitory action of cholera toxin was neither merely due to the increase in intracellular cAMP concentrations, nor to decrease in cell surface expression of the CD28 molecule. To evaluate the effects of cholera toxin on late events of Jurkat cell activation induced by CD28 and CD3 mAbs, the action of cholera toxin and cAMP and CD3- and CD28-mediated IL-2 secretion was analyzed. CD3-induced IL-2 secretion was highly sensitive to cholera toxin (ID less than 5 ng/ml); on the other hand, CD28-induced IL-2 secretion was poorly sensitive to cholera toxin, in sharp contrast to (Ca2+)i mobilization. On the basis of these data, it is hypothesized that the CD28 pathway could be associated with at least two distinct transduction mechanisms, one responsible for the (Ca2+)i rise in Jurkat cells and highly sensitive to cholera toxin, and the other, whose second messenger is unknown, resistant to cholera toxin and responsible for IL-2 secretion.

Antibodies, Monoclonal↗
PubMedDate not supplied

A biochemical analysis of the secregation of HLA-DR heavy and light chains in a family studied by two-dimensional gel electrophoresis.

Previous studies in our laboratory using primed lymphocyte typing (PLT) in an informative family have led to the identification of four traits and two regions, separable by recombination within the HLA-DR system. In the present study, we analysed the heterogeneity of HLA-DR antigens among members of this family as a first step towards defining the molecular entities responsible for the observed cellular reactivities. Cell lines of various genotypes derived from the members of this family were labelled biosynthetically with 35S-methionine. The total glycoproteins and immunoprecipitates prepared with two monoclonal anti-HLA-DR antibodies, two monoclonal anti-mouse Ia antibodies cross-reactive with HLA-DR, and a rabbit anti-HLA-DR (anti-p27,33) antiserum were fractionated by two-dimensional gel electrophoresis. In agreement with previous results, HLA-DR light chains were clearly polymorphic whereas the heavy chains looked rather monomorphic. The light chain subunits either segregated with one haplotype, or were shared by some but not all haplotypes or were common to all haplotypes. Whereas the haplotype-specific polypeptides correlated best with HLA-DR3 and HLA-DR5 specificities, the shared subunits may have corresponded to the cross-reactivities observed by PLT. Comparison of the patterns obtained with the various monoclonal antibodies and with the rabbit antiserum revealed that each monoclonal antibody bound a subset of HLA-DR light chains, all of which were present in the anti-p27,33 precipitates. This rabbit antiserum and one of the monoclonal antibodies immunoprecipitated a set of heavy chains not bound by the other 3 antibodies. Since overlapping pools of light chains were present in all five immunoprecipitates, these results suggest that different heavy chains may associate with the same light chains.

Animals↗
PubMedDate not supplied

Subcellular localization of class I (A,B,C) and class II (DR and DQ) MHC antigens in jejunal epithelium of children with coeliac disease.

Thin frozen sections of 11 jejunal biopsies from 10 children at different stages of coeliac disease were stained by immunofluorescence technique using a panel of anti-HLA class I (A, B, C) and anti-HLA class II (DR and DQ) monoclonal antibodies. On the epithelium of flattened mucosa, in contrast with control sections, the intensity of the labeling on the basolateral membranes with both anti-class I and class II DR antibodies decreased strongly from the bottom to the upper part of the crypts, and no bright patchy staining was observed on the apical part of enterocytes with anti-HLA DR antibodies. Numerous cells with large granules expressing class I and class II DR antigens were found in the epithelium of the small intestine. Children with a fully recovered mucosa expressed MHC antigens identical to those previously observed in normal epithelium. On the other hand, children with intermediate mucosal lesions showed the presence of MHC antigens in varying degrees. The results of this report indicate that immunological mechanisms may play a prominent role in coeliac disease.

Celiac Disease↗
PubMedDate not supplied

Differential immuno-suppressive effects of metabolic inhibitors on T-lymphocyte activation.

An important challenge in the field of auto-immune diseases, bone marrow and organ transplantation is the control of T-lymphocyte activation. To gain more insight into the in vitro correlation of immunosuppression, we investigated the effects of cyclosporin A (CSA) and two other metabolic inhibitors on cytokine secretion and T-cell proliferation. Secretion of TNF-alpha and GM-CSF was much more resistant to metabolic inhibitors than proliferation or synthesis of IL-1 alpha or IL-2. Moreover, our data suggested that the regulation of IL-1 alpha production in T-cells was CSA and protein kinase C (PKC)-dependent, as opposed to monocytes regulation. The receptivity to the epithelial cell-derived cytokine IL-7, associated either with antigen-dependent or independent triggering, was almost similarly inhibited by cyclosporin A, forskolin or PKC inhibitor, in sharp contrast to IL-2 receptivity. In this latter case, CD28+ IL-2 stimulation was more sensitive to both forskolin and PKC inhibition than that of CD2 or CD3+ IL-2. With regard to CSA effects, limiting dilution analysis provided evidence for some heterogeneity at the clonal level. This strongly suggested that T-cell functional monitoring at the population level does not truly reflect the actual immunosuppression. Additional experiments are required to evaluate the sensitivity to metabolic inhibitors of T-lymphocyte activation via the natural ligands of CD2 and CD28.

Antigens, CD↗