Influence of MHC class I molecules on T-cell proliferation induced by CD3 or Thy-1 stimulation.
We have reported that class I- [and lymphocyte function-associated antigen-1 (LFA-1-)] specific monoclonal antibodies (mAb) inhibit anti-CD3-mediated activation of naive T cells. The present study investigated the mechanism of this inhibition. CD28-specific mAb augmented stimulation induced by soluble CD3 mAb, but this costimulation was also inhibited by anti-class I or anti-LFA-1 mAb. However, stimulation of T cells was not inhibited when activated B cells were present. Neither B7-1- nor B7-2-specific blocking mAb or soluble CTLA-4, CD40 or gp39 restored the inhibition. Thus, other molecules expressed on activated B cells are implicated for T-cell activation, which could compensate blockade of class I or LFA-1 molecules. Inhibition induced by class I-specific mAb could potentially be mediated through extracellular, transmembrane or cytoplasmic domains of the target molecules. These possibilities were evaluated by the use of mice transgenic for the Qa-2 molecule, selected for expression of Qa-2 at levels equivalent to classical class I molecules. Qa-2 is inserted in the membrane through phosphatidylinositol linkages. Antibodies directed to Qa-2 inhibited CD3-induced stimulation, demonstrating that cytoplasmic and transmembrane protein sequences of class I molecules are not necessary for the inhibitory effect. Inhibition thus presumably depends on extracellular domains. Finally, T cells from beta 2-microglobulin knock-out mice responded to CD3-specific mAb as well as their class I-positive littermates. Nevertheless, stimulation of T cells from these mice with mitogenic anti-Thy-1 mAb was markedly reduced. Signalling by Thy-1 and the CD3 complex may normally occur through pathways in which class I molecules are implicated.
Amirayan
N
N
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Furrie
E
E
Deleuil
F
F
Mellor
A
A
Leserman
L
L
Machy
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018800:Thy-1 Antigens / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D016169:Lymphocyte Function-Associated Antigen-1; D018800:Thy-1 Antigens