Homotypic aggregation of CD103 (alpha E beta 7)+ lymphocytes by an anti-CD103 antibody, HML-4.
One monoclonal antibody, HML-4, directed against the alpha E beta 7 integrin (CD103), an integrin preferentially expressed on human intestinal intraepithelial lymphocytes (IEL), induced the homotypic aggregation of IEL and of a CD103+ MOLT16 cell line. Aggregation was an active adhesion event dependent on an intact cytoskeleton, on tyrosine phosphorylation but not on activation of protein kinase C. It was blocked by four other anti-CD103 antibodies but by none of the antibodies blocking known adhesion lymphocyte pathways. It was associated with a redistribution of the CD103 integrin in the areas of cell-cell contacts. These results indicated that HML-4-induced homotypic adhesion was mediated via CD103 and resulted from the binding of the integrin to an as yet undefined ligand expressed by CD103+ cells. This ligand was distinct from the epithelial ligand of CD103: in contrast with homotypic adhesion, heterotypic adhesion of CD103+ MOLT16 cells on two epithelial intestinal cell lines (DLD1 and HT29) was dependent on the presence of divalent cations, was not enhanced by HML-4, was inhibited by HML-1 but not by the three other antibodies with an inhibitory effect on homotypic adhesion. Finally, the study of conjugates between CD103+ and CD103- sublines derived from the MOLT16 cell line suggested that HML-4-induced homotypic aggregation resulted from homophilic CD103-CD103 interactions.
Benmerah
A
A
Développement Normal et Pathologique du Système Immunitaire, INSERM U 132, Hôpital Necker-Enfants Malades, Paris, France.
Badrichani
A
A
Ngohou
K
K
Mégarbané
B
B
Bègue
B
B
Cerf-Bensussan
N
N
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000939:Epitopes; D016023:Integrins