The lymphocyte function-associated antigen (LFA)-1 and CD2/LFA-3 pathways of antigen-independent human T cell adhesion.
Human cytotoxic T lymphocyte clones form conjugates with both antigen-positive and antigen-negative lymphoblastoid cells. Conjugates with antigen-negative targets form as rapidly, and are almost as frequent, as those with antigen-positive targets; both types are strong. Monoclonal antibodies against lymphocyte function-associated antigen (LFA)-1, CD2, and LFA-3 (or their Fab fragments) each consistently inhibit conjugate formation, but only partially; mixes of alpha LFA-1 with either CD2 monoclonal antibodies or alpha LFA-3 cause complete inhibition. Our previous studies have demonstrated two distinct pathways of antigen-independent conjugate (AIC) formation, one involving LFA-1 and the other involving CD2/LFA-3. The present studies showing supra-additive inhibition with mixes of Fab indicate that at least a major fraction of the conjugates involve T cells which utilize both pathways. Preincubation studies (and restricted expression for CD2) demonstrate that in the CD2/LFA-3 pathway, CD2 is critical on the effector and LFA-3 on the target and that in the LFA-1 pathway, LFA-1 is critical on the effector. Analysis of conjugate formation by primary allosensitized T cells confirms the critical findings made with T cell clones. Among a panel of antigen-negative "target" cell lines tested, there is wide variation in the number of AIC formed with cytotoxic T lymphocyte clones; this variation correlates partially with differences in level of expression of LFA-3. Both pathways of adhesion are utilized in AIC formation with all five targets tested, but there was variation between targets in the relative contribution by each pathway. Studies of inhibition of lysis (rather than conjugate formation) support the relevance of the two-pathway model to the lytic process as a whole. These studies demonstrate the general involvement of two pathways of adhesion in human T cell interactions: one involving T cell LFA-1 and the other involving T cell CD2 binding to target cell LFA-3.
Shaw
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Luce
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D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000502:physiology*; D002448:Cell Adhesion; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D016169:Lymphocyte Function-Associated Antigen-1