Antigen-specific and antibody-mediated growth inhibition of suppressor T cell hybridomas. Roles of H-2 and the CD3-T cell receptor-alpha/beta complex.
Eight different Ts cell hybridomas (including inducer (Ts1) and effector (Ts3) suppressor cells) specific for the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten were tested for their ability to respond to Ag or anti-CD3 antibody in a growth-inhibition assay. Results suggest that the expression of the TCR-CD3 complex on Ts hybridomas is required for the Ag or anti-CD3-mediated growth inhibition. One of the CD3+, Ts hybridomas (CKB-Ts3-9.H3) was tested in detail; this CD4- effector suppressor cell hybridoma showed specific inhibition of growth in the presence of NP or NIP-coupled protein conjugates but not in the presence of other irrelevant hapten-protein conjugates. In addition, growth of this hybridoma was specifically inhibited by anti-CD3 and anti-TCR-alpha/beta antibodies but not by control hamster antibodies. In order to study the role of MHC molecules in Ag-mediated growth inhibition, Ts cell hybridomas were incubated with Ag (NP-keyhole limpet hemocyanin) in the presence of spleen cells from various H-2 congenic strains. The results suggest that the Ts hybridomas that express donor Ts-derived TCR beta-chain recognize Ag in an MHC-restricted manner, whereas the two Ts3 hybridomas that utilize BW5147-derived TCR-beta recognize Ag in H-2 unrestricted way. Co-incubation of anti-CD3 and anti-TCR-alpha/beta antibodies with specific Ag enhanced the Ag-mediated growth inhibition, whereas anti-LFA-1 antibody completely blocked the Ag-mediated effect. The combined data suggest that, like Th hybridomas, expression of CD3-associated-TCR complex is essential for the Ag responsiveness of Ts cell hybridomas.
Kuchroo
V K
VK
Department of Pathology, Harvard Medical School, Boston, MA 02115.
Billings
P R
PR
Levine
C
C
Martin
C A
CA
Kubo
R T
RT
Dorf
M E
ME
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D000941:Antigens / Q000276:immunology*; D000943:Antigens, Differentiation / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017252:CD3 Complex; D006183:H-2 Antigens / Q000502:physiology*; D006825:Hybridomas / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D006183:H-2 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D016028:Receptors, Leukocyte-Adhesion