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

J Immunol. 1993 Jan 1;150(1):67-77.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Clone Cells / immunology
  • Clone Cells / metabolism
  • Dinitrophenols / immunology*
  • Gene Expression*
  • Genes, Immunoglobulin
  • Histocompatibility Antigens Class I / immunology*
  • Immunoglobulin Variable Region / genetics
  • 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

Substances

  • Dinitrophenols
  • Histocompatibility Antigens Class I
  • Immunoglobulin Variable Region
  • Receptors, Antigen, T-Cell, alpha-beta
  • Suppressor Factors, Immunologic