Immunologists agreed that an individual vertebrate synthesizes many millions of structurally different forms of antibody molecules even before it encounters an antigen.
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Some of the most significant advances in molecular biology have relied upon the methodology of genetics. The same statement may be made concerning our understanding of immunological phenomena.
What attracted me to immunology was that the whole thing seemed to revolve around a very simple experiment: take two different antibody molecules and compare their primary sequences.
The immune system has evolved the capacity to react specifically with a very large number of foreign molecules with which it had no previous contact while avoiding reactivity for autologous molecules, naturally antigenic in other species or in other individuals of the same species.
Moreover the incorporation requires the same components needed for protein synthesis, and is inhibited by the same inhibitors. Thus the system is most unlikely to be a complete artefact and is very probably closely related to genuine protein synthesis.
As biologists, we contemplate with admiration and awe the wondrous array of sophisticated cell interactions and recognitions evolved in the T cell immune system, which must be a model for other similarly complex biological systems of highly differentiated organisms.
Back in 1962, when I had by accident become the supervisor of Roberto Celis in Argentina, it occurred to me that antibody diversity might arise from the joining by disulphide bridges of a variety of small polypeptides in combinatorial patterns.
We know virtually all of the genes known to mammals. We do not know all of the combinations.
The study of the amino acid sequence around the disulphide bonds of the immunoglobulins was my own short-cut to the understanding of antibody diversity.
We found out that, contrary to what many people thought, in the immune system, genes can change during the life cycle of the individual.
In principle. what is done is to take the nucleus out of a cell with a very fine micro-pipette or needle and introduce it into an egg. That had been done with amphibians a long time ago, and then there was a long pause of many years before people were clever enough to make that work in the sheep.
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