Biomedical subjects
Publications and source records attributed to M L Gefter.
An analysis of recombinations between strains C57BL and BALB/c at the Igh locus suggest that only strains B X D20 and B X D27 recombined in this region. This implies that the maps of Igh markers in strains C57BL, DBA/2 and BALB/c resemble one another.
T lymphocytes produce a variety of immunoregulatory molecules including gamma interferon (IFN-gamma) and antigen-specific suppressor and enhancer factors. During our studies of active substances obtained from cloned T-cell lines, we observed that certain fractions administered to mice resulted in enhancement of immune responses. Preliminary characterization of the substance suggested that it could be IFN-gamma and we therefore undertook a study of the action of IFN-gamma produced by recombinant DNA methodology on immune responses. We found that for several antigens, administration of IFN-gamma to mice leads to two- to five-fold enhancement of antibody formation provided that the IFN-gamma and antigen are administered together. The effect was dose dependent, giving a maximal response at 500-600 anti-viral units per mouse. Preliminary studies suggest that the macrophage may be the target of IFN-gamma action. Addition of IFN-gamma to cultures of a macrophage cell line leads to a greater than 10-fold increase in the level of RNA coding for I-region-encoded cell surface molecules.
The heavy (H) and light (L) chains of antibodies consist of variable (V) and constant (C) regions. The V regions of the heavy and light chains form the antibody combining site. To determine whether a V region could be functional when joined to a polypeptide other than its own C region, we constructed a chimaeric gene encoding the V region of a mouse heavy chain and the C region of a mouse kappa light chain ( VHC kappa). The heavy-chain gene is derived from an A/J mouse hybridoma cell line 36-65 whose antibody product (gamma 1, kappa) is specific for the hapten azophenylarsonate. We report here that, when introduced into a mouse myeloma cell line, the chimaeric gene is expressed and a protein of the expected molecular weight is secreted into the medium. As light chains tend to dimerize we expected that the VHC kappa protein might associate with light chain from the cell line 36-65 to form an antibody-binding molecule. Affinity binding experiments and Ka determination indicate that this is the case. Dimers of this type offer a novel and interesting alternative to existing antibody-binding molecules.
T lymphocytes require a foreign antigen to be presented on a cell surface in association with a self-transplantation antigen before they can recognize it effectively. This phenomenon is known as major histocompatibility complex (MHC) restriction. It is not clear how an incalculably large number of foreign proteins form unique complexes with a very limited number of MHC molecules. We studied the recognition properties of T cells specific for a peptide derived from bacteriophage lambda cI protein. Analogues of this peptide, as well as peptides derived from other unrelated antigens which can be presented in the context of the same MHC molecule, can competitively inhibit activation of these T cells by the cI peptide. Furthermore, these unrelated antigens can stimulate cI-specific T cells if certain specific amino-acid residues are replaced. Here we suggest a model in which all antigens give rise to peptides that can bind to the same site on the MHC molecule. T-cell recognition of this site (which is presumed to be polymorphic) with or without antigen bound can explain self-selection in the thymus and MHC restriction.