Reconstitution of TCR alpha-chain expression in deletion mutants restores dinitrophenyl-specific/class I MHC-restricted suppressor molecule production.
A population of CD8+ T cells from dinitrobenzene sulfonate-primed mice produce soluble effector molecules that down-regulate the magnitude of dinitrophenol-specific contact hypersensitivity reactions. These soluble molecules express the binding specificity and serologic determinants of alpha/beta TCR. To examine the requirement for the TCR-alpha chain in the production of these molecules, we have cloned the alpha-chain gene used to encode the surface TCR of MTs 79.1, a T cell hybridoma producing a DNP/Kd-specific soluble suppressive molecule, and tested the ability of this gene to reconstitute the production of the regulatory molecule in TCR alpha-chain gene deletion mutants. Transfection and expression of the alpha-chain construct into an alpha-chain deletion mutant of the parental hybridoma that expressed the parental beta-chain gene resulted in reconstitution of both surface TCR expression and production of the soluble suppressive molecule. As with the molecule produced by the MTs 79.1 parental cells, the inhibitory activity produced by these alpha-chain gene transfectants was DNP-specific and expressed determinants bound by anti-V beta 8 Abs. Transfection of the alpha-chain gene construct into an alpha-/beta- chain gene deletion mutant did not restore the production of the soluble regulatory molecule. These results indicate that in addition to the TCR beta-chain gene, expression of the TCR alpha-chain gene is also required for the production of these molecules. Our results strongly support the hypothesis that some forms of immunosuppression are mediated by soluble forms of the TCR.
Barbo
J V
JV
Department of Immunology, Cleveland Clinic Foundation, OH 44195.
McCormack
J E
JE
Moorhead
J W
JW
Fairchild
R L
RL
D000818:Animals; D001483:Base Sequence; D003877:Dermatitis, Contact / Q000276:immunology; D004136:Dinitrobenzenes / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D017384:Sequence Deletion; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D014162:Transfection
D004136:Dinitrobenzenes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D013491:Suppressor Factors, Immunologic; C040234:1,2-dinitrobenzene