ABSTRACT

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Since their discovery at the end of the 19th century,

antibodies (Abs) have become important biological tools because of their multiple and versatile applications in basic research and their enormous potential as reagents for diagnosis, prophylaxis, and therapy. A convenient way of sensing this expectation is to consider the history of the Nobel Prize for Physiology or Medicine. The first Nobel laureate in this category was Emil von Behring “for his work on serum therapy … by which he has placed in the hands of the physician a victorious weapon against illness and deaths.” Since

then, 15 more Nobel Prizes have been awarded to individuals who have made significant contributions to immunology. On six occasions (P. Ehrlich in 1908, K. Landsteiner in 1930, R. Porter/G. Edelman in 1972, R. Yalow in 1977, G. Kohler/C. Milstein in 1984, and S. Tonegawa in 1987) those prizes were awarded to individuals whose research field was directly related to the antibody molecule. Polyclonal antibodies (“antisera”) were the protagonists during the period of serology and serotherapy. Monoclonal antibodies (mAbs) appeared in the mid-1970s to become the prime tools for powerful analytical techniques such as flow cytometry and immunoenzymatic assays. More recently, the advent of molecular biology and recombinant DNA techniques has made possible the creation of recombinant antibodies (rAbs). These artificial molecules are expected to fulfill hopes and needs in an area still elusive to more traditional Abs: the development of effective prophylactic, therapeutic, and

in vivo

diagnostic reagents for use in humans. Recombinant Ab technologies are a good example of how curiosity for understanding basic

phenomena has yielded information useful for inventing novel molecules of practical interest. For instance, an understanding of the composition, structure, and organization of the genetic complexes coding for Ab molecules in different species

has contributed to the development and application of methods for assembling an antigen (Ag) binding moiety of interest as a functional Ab molecule. Ag binding moieties are encoded by variable (V) genetic elements contained within these genetic complexes, and many have been expressed in the context of almost any desired human immunoglobulin (Ig) class or subclass.