Role of interaction of CD2 molecules with lymphocyte function-associated antigen 3 in T-cell recognition of nominal antigen.
The role of the interaction of CD2 molecules with lymphocyte function-associated antigen 3 (LFA-3) in facilitating nominal antigen recognition by T lymphocytes was studied by utilizing an HLA-DR4-restricted CD4+ cytotoxic human T-cell clone specific for human immunodeficiency virus envelope glycoprotein gp120 as a responder and murine fibroblasts transfected with human class II major histocompatibility complex (MHC) and/or human LFA-3 molecules as antigen-presenting cells (APC). Although expression of the DR4 restriction element in fibroblasts is sufficient for T-cell recognition of a gp120 peptide as judged by induction of proliferation coexpression of human LFA-3 on DR4+ APC decreases the molar requirement of nominal antigen by greater than one order of magnitude. Both LFA-3 and the relevant class II MHC molecules are necessary for antigen-independent conjugate formation, but the binding is further enhanced by specific nominal antigen. CD2-LFA-3 interaction is independent of T-cell receptor-MHC interaction and contributes directly to the stabilized conjugate between the T cell and LFA-3-bearing APC; soluble CD2 and monoclonal antibodies to LFA-3 and CD2 reduce T-cell-APC binding to the level mediated by nominal antigen and MHC. During conjugate formation, CD2 but not CD3 molecules are reorganized into the cell-cell interaction site in an antigen-independent manner. Thus, reorganization and/or coassociation of CD2 with CD3 molecules is not essential for T-cell activation.
Koyasu
S
S
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA.
Lawton
T
T
Novick
D
D
Recny
M A
MA
Siliciano
R F
RF
Wallner
B P
BP
Reinherz
E L
EL
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D018801:CD2 Antigens; D018968:CD58 Antigens; D002450:Cell Communication; D002478:Cells, Cultured; D002999:Clone Cells; D006801:Humans; D007365:Intercellular Junctions / Q000276:immunology; D007739:L Cells / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic