DNP-specific/class I MHC-restricted suppressor molecules bear determinants of the T cell receptor alpha- and beta-chains. The V beta 8+ chain dictates restriction to either K or D.
To examine in greater detail the relationship between DNP-specific/class I MHC-restricted suppressor molecules (SSF) that inhibit contact sensitivity to 2,4-dinitrofluorobenzene and the receptors on the T cells that produce them, we have generated two T cell hybridomas that can be induced to produce and secrete these molecules. In order to become activated to produce SSF, the Ts 15.15 and 15.31 cells required recognition of complexes of DNP/Dd on presenting cells. The suppressor molecules produced by each of the Ts hybrids had the same specificity, recognizing DNP/Dd on cells in the immune lymph node cell target population. The activation of the Ts hybrids was blocked when the cells were treated with the anti-V beta 8 antibody F23.1 before coculture with the DNP-presenting cells. Reduction of the 15.15 and 15.31 SSF followed by affinity chromatography on DNP-bovine-gamma-globulin-Sepharose beads indicated that these molecules are dimers and that one of the chains (Ag-binding(AgB] binds to cellfree DNP and one (non-Ag-binding (NAgB) chain) does not. The AgB chain was found to express an epitope bound by a mAb specific for a TCR alpha-chain-constant region determinant. Alternatively, the NAgB chain expressed an epitope bound by the anti-V beta 8 mAb F23.1. Active hybrid suppressor molecules were generated by combining the NAgB chain from a DNP-specific/H-2Kd-restricted SSF (produced by Ts hybridoma 3-10) with the AgB chain from Ts 15.31 and by combining the NAgB chain from Ts cell 15.15 with the 3-10 AgB chain. In each case, the class I MHC element (i.e., Kd or Dd) restricting the activity of these hybrid SSF correlated with the source of the V beta 8+, NAgB chain. Thus, these secreted immunoregulatory molecules have the Ag/MHC specificity of the T cells producing them and are structurally and serologically related to the TCR-alpha/beta. The results further suggest that for some hapten-specific/class I MHC-restricted TCR, the alpha-chain may have avidity for the hapten and the beta-chain may dictate the MHC restriction element (K or D) recognized by the receptor.
Fairchild
R L
RL
Department of Immunology/Microbiolog, University of Colorado School of Medicine, Denver 80262.
Kubo
R T
RT
Moorhead
J W
JW
D000818:Animals; D004136:Dinitrobenzenes / Q000276:immunology; D000939:Epitopes; D006183:H-2 Antigens / Q000276:immunology*; D006825:Hybridomas; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013491:Suppressor Factors, Immunologic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D004136:Dinitrobenzenes; D000939:Epitopes; D006183:H-2 Antigens; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013491:Suppressor Factors, Immunologic