A monoclonal antibody to LFA-3, the CD2 ligand, specifically immobilizes major histocompatibility complex proteins.
T cells are activated when the antigen-specific T cell receptor recognizes antigen in association with major histocompatibility complex (MHC) proteins. The T cell surface protein CD2 (T11, LFA-2, the T erythrocyte receptor) and its target or stimulator cell ligand, lymphocyte function-associated antigen-3 (LFA-3), are also involved in T cell adhesion and activation. The molecular mechanisms by which the CD2/LFA-3 interaction affects T cell adhesion and activation are unclear. The CD2/LFA-3 interaction may be modeled by the interaction between LFA-3 and anti-LFA-3 monoclonal antibody (mAb). We used the fluorescence photobleaching recovery technique to investigate the effect of anti-LFA-3 mAb on the lateral mobility of MHC proteins in plasma membranes of JY, a human Epstein-Barr virus-transformed B cell line. Anti-LFA-3 mAb induced immobilization of class I MHC proteins labeled with bivalent but not monovalent fluorescein-conjugated W6/32 mAb. Anti-LFA-3 mAb also caused immobilization of class II MHC proteins labeled with bivalent fluoresceinated LB3.1 mAb. In contrast, anti-LFA-3 mAb did not affect the mobilities of either a B cell membrane protein labeled with bivalent fluoresceinated anti-CD45 (human leukocyte antigen) mAb or a membrane lipid analogue. Unlike anti-LFA-3 mAb, anti-LFA-1 mAb did not affect class I MHC protein mobility. These results suggest that CD2 binding to LFA-3 may trigger a physiological response in which target cell MHC proteins, cross-linked by receptors on the T cell surface, are immobilized at and thereby localized to the T cell-target cell interface.
Bierer
B E
BE
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
Golan
D E
DE
Brown
C S
CS
Herrmann
S H
SH
Burakoff
S J
SJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000943:Antigens, Differentiation / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D018801:CD2 Antigens; D018968:CD58 Antigens; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D008285:Major Histocompatibility Complex; D008560:Membrane Fluidity; D008562:Membrane Glycoproteins / Q000502:physiology*; D008563:Membrane Lipids / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D018968:CD58 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D011971:Receptors, Immunologic