PubMed · 4181433
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G Kronvall, R C Williams. 1969. Immunologic "short circuits".. https://doi.org/10.7326/0003-4819-70-5-1043
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Some of the problems caused by malaria, which places a huge roadblock in front of economic progress in the Third World, may be solved by a new vaccine created by Dr. Manuel Patarroyo, a Columbian physician and researcher. "Imagine how things would be if Canadians had malaria," he says. "Episodes last 10 days, then there are 10 days of recovering. This leaves only 10 days each month in which to do some productive work. Then imagine killing the population of Toronto each year, and you can see the huge toll in terms of the number of yearly deaths globally from malaria." His discovery also raises the issue of "intellectual racism" because of criticism of Patarroyo's methods by Western scientists. Patarroyo, meanwhile, turned down a $60-million offer for his vaccine, and instead donated the patent to the World Health Organization.
Molecular interactions between the human insulin molecule and a panel of seven monoclonal antibodies (mAbs) against insulin were investigated by surface plasmon resonance. Using real-time analysis (BIAcore technology), the antigenic sites recognized on the human insulin molecule by these mAbs were mapped. Three overlapping regions could be defined on the insulin molecule coupled to the dextran matrix on the basis of its recognition by three mAbs groups: group I (mAbs 19, 10), group II (mAbs 13, 5, 25, 15) and group III (mAb P10). The antigenic determinants of the molecule in solution were mapped using a two-site assay in which insulin was presented to each mAb, bound to a rabbit anti-mouse IgG Fc gamma 1 coupled to the dextran. Four antigenic regions were defined: regions I and III were defined by the same antibodies as above whereas region II was recognized differently by mAbs 13, 5 (region IIa) and mAbs 25,15 (region IIb). The Ka value of the mAbs determined using the BIAcore were in the same range (from 3 x 10(7) M-1 to 6.6 x 10(9) M-1) whether insulin was coupled to the dextran matrix or in solution. Furthermore, mAbs 19 and P10, which recognize two distinct regions on the insulin molecule, were selected to develop a highly sensitive immunoassay for measurement of insulin in serum.
Mature T cells may be produced in the thymus, or by expansion in the periphery. While thymus output of virgin cells ensures repertoire diversity, peripheral expansion increases the size of rare clones, and thus the efficiency of immune responses. We studied the role of both phenomena in the generation of the CD8+ T cell pool using RAG-/- female mice expressing a transgenic T cell receptor specific for the male antigen; nude mice injected with peripheral T cells; and euthymic irradiated chimeras injected with bone marrow and mature T cells. Our results show that the total number of virgin and activated T cells, each constituting about half of the peripheral T cell pool, was regulated independently, revealing an efficient mechanism to maintain repertoire diversity while optimizing the immune response.