Tolerance to self antigens shapes the T-cell repertoire.
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A M Pullen
Publications and source records attributed to A M Pullen.
The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens.
T cells with V beta 3+ alpha beta receptors are deleted by self-tolerance in mice with particular major histocompatibility complex/self-antigen combinations. This also occurs for other V beta elements. Polymorphism in the major histocompatibility complex and/or the self-antigens that cause massive deletion of T cells using particular V beta elements may be maintained by the need to balance the advantage of a diverse T-cell repertoire against the potential involvement of those elements in autoimmune disease.
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Fetal calf serum stimulates 'autoreactive' T-cell hybridomas.
During attempts to generate Sendai virus-specific T-cell hybridomas, a number of autoreactive T-cell hybridomas were produced. These hybrids secrete IL-2 in response to class II-positive syngeneic cells in the absence of added Sendai virus. Class II molecules on the stimulator cells are involved since monoclonal anti-class II antibodies block the reaction, and mapping studies using recombinant mouse strains show the response is class II restricted. Hybridomas adapted to grow in serum-free medium do not respond to syngeneic cells in the absence of serum; however, addition of fetal calf serum (FCS) restores the response. The component of FCS responsible for the stimulation of the hybridomas has been partially purified and characterized, and its mode of action investigated. These findings suggest that the putative 'autoreactive' T-cell hybridomas reported by others may be specific for a component of the culture medium rather than being truly self-reactive.
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"Auto-reactive" T-cell hybridomas and the role of foetal calf serum.
A panel of "auto-reactive" T-cell hybridomas has been generated by fusing Sendai virus-primed, Peyer's patch T cells from CBA mice with BW 5147. The hybridomas produce Il-2 in response to stimulation by Class II-positive syngeneic cells in the absence of added Sendai virus. The stimulator genes for two hybridoma clones have been mapped using recombinant mouse strains and the restriction has been confirmed by inhibition with monoclonal anti-Class II antibodies. Hybridomas grown in serum-free medium do not respond to syngeneic cells in the absence of foetal calf serum (FCS) and the response is restored by the addition of FCS, but not bovine serum albumin (BSA), normal mouse serum or Sendai virus. The component of FCS which is required for stimulation of the hybridomas has been partially purified and characterised. Its mode of action has been investigated and it acts on the stimulator cells and not on the hybridomas.
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Citrate synthase: an immunochemical investigation of interspecies diversity.
Rabbit antibodies have been raised to pig heart citrate synthase. Using purified IgG, competitive enzyme-linked immunoassays and assays of citrate synthase activity indicate the presence of antibodies to a number of antigenic sites on the enzyme, only some of which are essential for catalytic activity. From a comparison of citrate synthases from prokaryotic and eukaryotic organisms, the degree of interaction between antibody and enzyme was in the order: pig heart greater than pigeon breast greater than Bacillus megaterium greater than Escherichia coli. These findings are discussed in terms of the known interspecies diversity of the enzyme.
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