The CD2 ligand LFA-3 activates T cells but depends on the expression and function of the antigen receptor.
The T cell Ag receptor (CD3/Ti) and the sheep E receptor (CD2) expressed on the surface of human T cells are both capable of initiating intracellular signals necessary for T cell activation. CD3/Ti interacts with Ag to initiate cellular immune responses. Although the exact function of CD2 is unknown, lymphocyte function-associated Ag 3 (LFA-3), a 55- to 70-kDa receptor expressed on a broad spectrum of hemopoietic and nonhemopoietic cells, has recently been shown to be its natural ligand. We show here that although purified multimeric LFA-3 is not capable of initiating transmembrane signaling events on its own, the combination of LFA-3 and the anti-CD2 mAb CD2.1 induces intracellular calcium increases, phosphatidylinositol second messenger generation and lymphokine secretion in the T cell leukemic line Jurkat. In order to study the signaling requirements of CD2, we compared the ability of CD2 mAb and LFA-3 to initiate activation signals in Jurkat and in three Jurkat-derived mutants. A CD3-CD2+ mutant failed to increase calcium or exhibit phosphatidylinositol hydrolysis to either the combination of agonist CD2 mAb 9-1 and 9.6 or LFA-3 and CD2.1. Reconstitution of the Ag receptor by transfection of the Ti-beta-chain restored the expression of the CD3/Ti complex and the ability to respond to either combination of CD2 ligands. However, no response to CD2 ligands was detected in a CD3+CD2+ mutant selected for signaling defects to CD3/Ti ligands. Complementation of the CD3/Ti signaling defect by cell fusion also restored competency to respond to CD2 agonists. These results demonstrate that LFA-3 under appropriate conditions can activate T cells via the CD2 complex and that this activation requires not only the cell surface expression of the CD3/Ti complex but also a functional Ag receptor pathway.
Bockenstedt
L K
LK
Division of Rheumatology and Clinical Immunology, University of California, San Francisco.
Goldsmith
M A
MA
Dustin
M
M
Olive
D
D
Springer
T A
TA
Weiss
A
A
D000276:Adjuvants, Immunologic / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D018801:CD2 Antigens; D018968:CD58 Antigens; D002118:Calcium / Q000096:biosynthesis; D002460:Cell Line; D004357:Drug Synergism; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D015290:Second Messenger Systems; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D002118:Calcium