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.
Int Immunol
; 8(2): 267-74, 1996 Feb.
Article
en En
| MEDLINE
| ID: mdl-8671612
ABSTRACT
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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Linfocitos B
/
Activación de Linfocitos
/
Linfocitos T CD4-Positivos
/
Antígenos HLA-DR
/
Antígenos CD4
Límite:
Humans
Idioma:
En
Revista:
Int Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
1996
Tipo del documento:
Article
País de afiliación:
Francia