Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the ability of a peptide mimicking the major binding site of HLA-DR beta 2 for CD4 (i.e. amino acids 134-148) to inhibit the adhesion of CD4+ T cells to B cells and ICAM-1-DR-expressing fibroblasts, as well as the proliferation of TCR-CD3-triggered CD4+ T cells. Peptide DR134-148 blocked CD4+ T cell (but not CD8+ T cell) binding to B cells and to DR+ ICAM-1+ fibroblasts in a concentration-dependent manner. A peptide composed of randomly associated identical amino acid residues had no effect. This inhibitory activity was not additive with the effect of an anti-CD4 antibody, peptide DR35-46 (mimicking another potential binding site of HLA-DR beta 1 to CD4) or an anti-LFA-1 antibody. Adhesion of a T cell line (HUT78) expressing a mutated form of CD4 unable to bind p56lck cytosine kinase was not inhibited by peptide DR134-148. In addition, herbimycin A, a tyrosine kinase inhibitor, abrogated the inhibitory activity of DR134-148. Since CD4-MHC class II interactions have been shown to play no detectable role in mediating antigen-independent adhesion in this assay, peptide interactions with CD4 may trigger an off signal down-regulating LFA-1-mediated adhesion. Indeed, adhesion of CD4+ T cells to ICAM-1- fibroblasts was not inhibited by peptide DR134-148, while the same peptide inhibited antigen (protein-pure derivative)- and anti-CD3 antibody-induced CD4 T cell proliferation. These findings suggest that the major sequence involved in the MHC class II interaction with CD4 is sufficient to induce a downstream negative regulatory signal that is mediated by p56lck, independently of antigen-specific TCR triggering.
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PMID:A synthetic peptide mimicking the HLA-DR beta 2-binding site for CD4 inhibits antigen-independent CD4+ T cell adhesion to B cells and CD4+ T cell activation. 867 12