Production of DNP-specific/class I MHC-restricted suppressor molecules is linked to the expression of T cell receptor α- and β-chain genes

• Published in: The Journal of immunology (1950) Vol. 150; no. 1; pp. 67 - 77
• Main Authors: FAIRCHILD, R. L, PALMER, E, MOORHEAD, J. W
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Association of Immunologists 1993
• Subjects: Animals; Biological and medical sciences; Clone Cells - immunology; Clone Cells - metabolism; Dinitrophenols - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Genes, Immunoglobulin; Histocompatibility Antigens Class I - immunology; Immunobiology; Immunoglobulin Variable Region - genetics; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred BALB C; Mutation; Receptors, Antigen, T-Cell, alpha-beta - genetics; Sequence Deletion; Suppressor Factors, Immunologic - biosynthesis; Suppressor Factors, Immunologic - genetics; Suppressor Factors, Immunologic - immunology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T cell receptor; Immunomodulation; Major histocompatibility system; Rodentia; Beta-Peptide chain; H-2-System; Hapten; Vertebrata; Specificity; Mammalia; Gene; Mouse; T-Lymphocyte; Alpha-Peptide chain; Suppressive cell; Class I histocompatibility antigen
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.150.1.67

The hapten/class I MHC-specific soluble immunoregulatory molecules produced by CD8+T cells from dinitrobenzene sulfonate-primed mice express the binding specificity and serologic determinants of alpha/beta TCR. To examine the genes used to encode these soluble immunoregulatory molecules, we utilized a surface TCR expressing Ts hybridoma, which constitutively produces a DNP/Kd-specific regulatory molecule. Northern and Southern analyses indicated that MTs 79.1 cells use a V beta 8 and a V alpha 4 gene to encode the variable regions of the surface alpha/beta TCR. A panel of TCR- variants was generated by subjecting MTs 79.1 cells to gamma-irradiation. Twelve of the TCR- variants were chosen for detailed characterization. Northern blot analyses indicated the absence of the MTs 79.1 V alpha 4 chain transcript in five of the variants and the absence of the parental V beta 8 chain transcript in the other seven. Southern blot analyses demonstrated the deletion of the parental gene encoding the alpha- or beta-chain from the genome of the respective mutant. None of the 12 TCR gene deletion mutants produced the parental suppressive activity. Expression of the parental TCR beta-chain gene in one of the beta-chain gene deletion mutants reconstituted the ability to produce this activity. As with the MTs 79.1 molecule, the regulatory molecule produced by the beta-chain gene transfectant was bound by and eluted from Sepharose columns coupled with either DNP or anti-V beta 8 antibodies. These results establish a strong linkage between the suppressor molecules produced by these Ts and TCR alpha- and beta-chain gene transcription.