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B Schraven

Publications and source records attributed to B Schraven.

61 records · Page 4Linked to original sources

Triggering of the alternative pathway of human T cell activation involves members of the T 200 family of glycoproteins.

The present report describes functional characteristics of a monoclonal antibody (mAb), TA/211, which is reactive with a common determinant of the human CD45 molecules. When added to purified testing human T cells, TA/211, which is itself not mitogenic, leads to a strong proliferative response in combination with submitogenic concentrations of anti-T11(2) plus anti-T11(3) mAb. Interestingly, while amplifying anti-CD2-mediated immune responses, T cell activation induced through triggering of the CD3 molecule is not enhanced by TA/211, indicating that the triggering signal provided through CD45 is restricted to alternative pathway activation. Employing T cell subsets negatively selected for the expression of CD45R molecules defined by the mAb anti-2H4 or UCHL1, respectively, it is demonstrated that resting T cells expressing the 2H4 molecules proliferate much stronger to TA/211 than the UCHL1+ T cell subset. Together with the finding that the 2H4+ T cell subset can be activated by the concomitant binding of anti-CD2 antibodies plus anti-2H4, these data strongly suggest that the high molecular weight species of CD45 expressed by unprimed T cells are themselves involved in T cell activation via the alternative pathway.

Adjuvants, Immunologic↗

The alternative pathway of T cell activation: biology, pathophysiology, and perspectives for immunopharmacology.

The application of monoclonal antibodies and recombinant mediators to studies of T cell activation has led to a new concept regarding the central mechanisms underlying specific immune responses in man. Stimulation of human T cells to express their functional programs with regard to immunoregulatory activities and effector functions can be mediated through several distinct mechanisms or pathways. We report on the recently discovered T3-Ti antigen receptor independent mode of human T cell activation, namely, the T11-mediated "alternative pathway." Recent evidence supports the notion that this pathway plays an important role in the immune response in man and that failure to activate T cells through T11 is associated with immunodeficiency. The characterization of functional epitopes of the T11 molecule along with functional investigations on patients suffering from etiologically different cases of immunodeficiency provides important perspectives for future pharmacological interventions into the human immune system. It seems likely that immunologic disorders such as autoimmune disease and immunodeficiencies result from overamplification or blockades of the "alternative pathway of T cell activation" and that the T11 epitope represents a potential site for selective inhibition of the "alternative pathway of T cell activation," e.g., by means of synthetic peptide analogues. Conversely, high affinity ligands to the T11 epitope might be suitable for immunostimulation immunodeficiencies that result from circulating blocking factors of the LFA-3/T11 interaction.

Animals↗

Developmentally regulated expression of the transmembrane adaptor protein trim in fetal and adult T cells.

TRIM is a recently identified transmembrane adaptor protein which is exclusively expressed in T cells and natural killer (NK) cells. In peripheral blood T cells TRIM has been reported to coprecipitate, comodulate, and cocap with the T-cell receptor (TCR), suggesting that it is an integral component of the TCR/CD3/zeta complex. Here we investigate the expression of TRIM mRNAs and proteins in developing thymocytes. Two splicing isoforms with open reading frames are observed, namely a full length (TRIM) and a truncated version (DeltaTM-TRIM). The latter lacks the extracellular and transmembrane domains as well as the first 10 cytoplasmic aminoacids and is significantly expressed only as mRNA in early fetal thymocytes. TRIM mRNA is detected in all mainstream thymocyte subsets in adult mice. TRIM protein, in contrast, first appears in the DN2 (CD44+ CD25+) subset of adult double negative (DN) cells. In fetal thymocyte development, TRIM mRNA is seen from dg 14.5 onwards whereas TRIM protein appears first on dg 16.5. In contrast to the adult, the TRIM protein was seen in a subset of fetal DN1 cells. In fetal and adult thymocytes, TRIM protein expression was highest in DN2, DN3 (CD44-25+) and in DP cells, compatible with a functional role at or around phases of thymic selection.

Adaptor Proteins, Signal Transducing↗

CD148.

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Amino Acid Sequence↗

CD2.

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Amino Acid Sequence↗