The role of the murine L3T4 molecule in T cell activation: differential effects of anti-L3T4 on activation by monoclonal anti-receptor antibodies.
MHC restricted T cells can be divided into two subsets based on the mutually exclusive expression of the cell surface differentiation antigens L3T4 and Lyt-2 in the mouse. Expression of the L3T4 marker is correlated most strictly with recognition of foreign antigen in association with self class II MHC molecules, or Ia molecules. Less stringently correlated with L3T4 expression is the recognition of unmodified self or non-self Ia molecules. Finally, expression of L3T4 is also correlated with certain functional properties, although this correlation is even less stringent. The major correlation for function is between L3T4 and the ability to activate B cells. These correlations have led to the hypothesis that L3T4 recognizes Ia molecules, and plays a role in increasing the affinity of T cell:Ia bearing cell interactions. This hypothesis is bolstered by the finding that anti-L3T4 antibody blocks such interactions. Recently, we and others proposed a second effect of cross-linking L3T4 molecules, namely negative signalling. We further proposed that the natural ligand for L3T4 is Ia molecules, and that Ia-driven cross-linking of L3T4 molecules on the T cell in the absence of receptor aggregation would lead to off signalling to the T cell and separation of cell conjugates. To better understand the role of the L3T4 molecule in T cell activation, we have examined the effect of several anti-L3T4 antibodies on stimulation of a cloned line of helper T cells by a panel of monoclonal antibodies directed at what appear to be different epitopes on the T cell receptor. Unlike previous analyses of stimulation of helper T cells with anti-T cell receptor antibodies, we observe differential effects of anti-L3T4 on T cell activation by anti-receptor antibodies, the effect of anti-L3T4 depending on the characteristics of the anti-receptor antibody. This result suggests that L3T4 is intimately associated with the T cell receptor, and may thus play a critical role in T cell specificity as part of the antigen:Ia recognition complex. This proposed role is in keeping with the very strong correlation between L3T4 expression and recognition of self class II MHC molecules. While these studies do not provide definitive evidence for a physical association between L3T4 and the T cell receptor, they do place certain constraints on current models and suggest new possibilities for understanding T cell recognition and development.(ABSTRACT TRUNCATED AT 400 WORDS)
Janeway
C A
CA
Department of Pathology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.
Haque
S
S
Smith
L A
LA
Saizawa
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell