An insight into the T-cell recognition system using antigen-specific functional T-cell lines.
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Biomedical subjects
Publications and source records attributed to E Mozes.
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Neonatal lupus erythematosus (NLE) syndrome is a result of the transfer of autoantibodies produced by the mother, across the placenta, to the fetus. NLE is characterized by a transient dermatitis, a variety of systemic and hematological abnormalities, and isolated cases of congenital heart block. The latter has been reported to be due to the presence of autoantibodies specific to La (SS-B) and/or Ro (SS-A). As female mice with experimental SLE, induced by immunization with the monoclonal anti-DNA 16/6 Id, produce a variety of autoantibodies including anti-Ro and anti-La antibodies, we examined the relevance of NLE in the murine system. Offspring of SLE-afflicted BALB/c mothers possessed antibody titers to the 16/6 Id, ssDNA, and nuclear extract, which gradually declined until reduced to normal levels by day 60 after delivery. Antibody titers in the sera of the mothers remained elevated throughout this period. Electrocardiograms were recorded from groups of neonates from mothers with experimental SLE. The results indicated that a high percentage of the offspring had defects in their conduction system including first, second, and third degree heart block; significant bradycardia; and wide QRS complex. Normal patterns were observed in offspring of healthy mothers. Experiments done with mice that were exposed to SLE-related autoantibodies early in their development indicated that offspring to mothers with experimental SLE were neither protected nor more susceptible to disease induction by the 16/6 Id.
Antigen-specific T-cell helper factors were secreted from a (T,G)-A--L specific T-cell line and clones. The factors were released upon antigenic stimulation and could be induced by a low or a high dose of antigen. The factors secreted upon low-dose stimulation possessed the antigenic specificity of the secreting cells, while the high dose-induced factors had a broader antigenic specificity and could react with the closely related polypeptide (Phe,G)-A--L, even when the cells were restricted to (T,G)-A--L. Both the low dose- as well as the high dose-induced factors could not trigger antibody production in the presence of a non-relevant antigen, and did not collaborate with B cells immunized with a non-related antigen for the production of antibodies. The helper factors, like their secreting cells, were H-2-restricted in the collaboration with B cells. In contrast to the helper cells, however, they did not require accessory cells for triggering the B cells in the process of antibody production. Some preparations of helper factors were found to be inactive. The helper activity could be restored by IL-2. Thus, IL-2 is an additional essential factor required for the antigen-specific collaboration of B cells and T-cell helper factors.
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The effect of a water soluble adjuvant (WSA) extracted from mycobacteria on the immune response to synthetic polypeptides has been studied in rabbits and inbred mice. WSA increased the antibody response of rabbits to the synthetic polypeptide poly(Tyr,Glu)-poly(DLAla)--poly(Lys) designated (T,G)-A--L when injected together with either incomplete or complete Freund's adjuvants (FIA or FCA). As compared to the respective controls, the effect of WSA was more pronounced when injected with FIA. No detectable antibody titre was observed in rabbits immunized with (T,G)-A--L and WSA administered in an aqueous medium. WSA had no enhancing adjuvant effect on the antibody response of C3H.SW high responder mice to (T,G)-A--L when given either with FIA or with FCA. However, the antibody titres of C3H/HeJ and SJL low responder mice to (T,G)-A--L were increased by WSA when injected in combination with FIA or FCA. The immune responses of mice to two other synthetic polypeptides poly(Phe,Glu)-poly(DLAla)--poly(Lys), designated (Phe,G)-A--L, and poly-(Tyr,Glu)-poly(Pro)--poly(Lys), designated (T,G)-Pro--L, were not affected by the addition of WSA. Thus, WSA "corrects" selectively the genetic defect of low responder mice to synthetic antigens.