Cell adhesion mediated by CD4 and MHC class II proteins requires active cellular processes.
Human CD4 is an accessory molecule found on the cell surface of a subset of T lymphocytes. We have previously shown by infection of simian fibroblasts with an SV40-CD4 recombinant virus that CD4 acts as an adhesion molecule by binding to human MHC class II Ag expressed on the surface of human B lymphocytes. This report confirms that human B lymphoblastoid cell lines expressing class II molecules at the cell surface can bind to Chinese hamster ovary cells that have been stably transfected with human CD4. This cellular adhesion is a late event, which is first detected after 2 h, but remains stable for up to 16 h. The association between CD4 and class II is energy dependent, as it is detected at 37 degrees C, but not at 4 degrees C or if either cell type is fixed with paraformaldehyde. ATP is required for the establishment and maintenance of stable CD4/class II-mediated cell conjugates. Cytoskeletal interactions also regulate CD4/class II adhesion as treatment with the microtubule and microfilament inhibitors colchicine, cytochalasin-D, and nocodazole rapidly dissociates even preformed cell conjugates. Our observations also indicate that the Ag-independent engagement of class II by CD4 induces homotypic clustering of human B cells. This effect is blocked by reagents directed against lymphocyte function-associated Ag-1 and may result from the induction of a high affinity phenotype of lymphocyte function-associated Ag-1 induced by class II signaling. Finally, we discuss the implications of CD4/class II-mediated adhesion and the role of CD4 in the regulation of T cell adhesion.
Kinch
M S
MS
Department of Immunology, Duke University Medical Center, Durham, NC 27710.
Strominger
J L
JL
Doyle
C
C
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D015704:CD4 Antigens / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D003599:Cytoskeleton / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D014162:Transfection
D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D000968:Antimycin A