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Homotypic aggregation of CD103 (alpha E beta 7)+ lymphocytes by an anti-CD103 antibody, HML-4
A Benmerah1, A Badrichani, K Ngohou
1Développement Normal et Pathologique du Système Immunitaire, INSERM U 132, Hôpital Necker-Enfants Malades, Paris, France.
Insights
Monoclonal antibody HML-4 triggers homotypic aggregation of intestinal lymphocytes via alpha E beta 7 integrin (CD103) interactions. This adhesion mechanism involves CD103 binding to an unknown ligand on CD103+ cells, distinct from epithelial cell interactions.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Intestinal intraepithelial lymphocytes (IEL) express alpha E beta 7 integrin (CD103).
- CD103 plays a role in lymphocyte adhesion and homing within the gut.
- Understanding CD103-mediated adhesion is crucial for immune responses in the intestine.
Purpose of the Study:
- To investigate the mechanism of homotypic aggregation induced by the anti-CD103 antibody HML-4.
- To identify the ligand involved in CD103-mediated homotypic adhesion.
- To differentiate CD103 homotypic adhesion from heterotypic adhesion to epithelial cells.
Main Methods:
- Utilized monoclonal antibody HML-4 against alpha E beta 7 integrin (CD103).
- Induced and analyzed homotypic aggregation of IEL and CD103+ MOLT16 cell lines.
- Investigated adhesion mechanisms involving cytoskeleton, tyrosine phosphorylation, and protein kinase C.
- Studied heterotypic adhesion of CD103+ cells to intestinal epithelial cell lines (DLD1, HT29).
- Examined conjugates between CD103+ and CD103- sublines.
Main Results:
- HML-4 induced homotypic aggregation of CD103+ cells, dependent on cytoskeleton and tyrosine phosphorylation.
- Aggregation was blocked by other anti-CD103 antibodies but not by antibodies for known lymphocyte adhesion pathways.
- CD103 redistributed to cell-cell contact areas during aggregation.
- Homotypic adhesion involved a CD103 ligand distinct from the epithelial ligand.
- Heterotypic adhesion to epithelial cells required divalent cations and was inhibited by HML-1.
- Homotypic aggregation likely resulted from homophilic CD103-CD103 interactions.
Conclusions:
- HML-4-induced homotypic adhesion is mediated by CD103 through interaction with an undefined ligand on CD103+ cells.
- This homotypic adhesion pathway is distinct from CD103-mediated heterotypic adhesion to intestinal epithelial cells.
- Homophilic CD103-CD103 interactions are suggested as the mechanism for HML-4-induced homotypic aggregation.
Abstract:
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.
