Relevance of CD6-mediated interactions in T cell activation and proliferation.
CD6 is a cell surface receptor expressed on immature thymocytes and mature T and B1a lymphocytes. The ultimate function of CD6 has not been deciphered yet, but much evidence supports a role for CD6 in T cell activation and differentiation. In this study, we show that a fraction of CD6 molecules physically associates with the TCR/CD3 complex by coimmunoprecipitation, cocapping, and fluorescence resonance energy transfer experiments. Image analysis of Ag-specific T-APC conjugates demonstrated that CD6 and its ligand, activated leukocyte cell adhesion molecule (CD166), colocalize with TCR/CD3 at the center of the immunological synapse, the so-called central supramolecular activation cluster. The addition of a soluble rCD6 form significantly reduced the number of mature Ag-specific T-APC conjugates, indicating that CD6 mediates early cell-cell interactions needed for immunological synapse maturation to proceed. This was in agreement with the dose-dependent inhibition of CD3-mediated T cell proliferation induced by soluble rCD6. Taken together, our data illustrate the important role played by the intra- and intercellular molecular interactions mediated by CD6 during T cell activation and proliferation processes.
Gimferrer
Idoia
I
Servei d'Immunologia, Hospital Clínic i Provincial de Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Calvo
Maria
M
Mittelbrunn
María
M
Farnós
Montse
M
Sarrias
Maria Rosa
MR
Enrich
Carlos
C
Vives
Jordi
J
Sánchez-Madrid
Francisco
F
Lozano
Francisco
F
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000276:immunology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015153:Blotting, Western; D017252:CD3 Complex / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D006801:Humans; D007152:Immunologic Capping / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D020410:Activated-Leukocyte Cell Adhesion Molecule; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D018956:CD5 Antigens; C062279:CD6 antigen; D011948:Receptors, Antigen, T-Cell