Читать книгу Immunology - Richard Coico - Страница 28

The most recent tidal surge in immunological research represents a triumph of the marriage of molecular biology and immunology. While cellular immunology had delineated the cellular basis for the existence of a large and diverse repertoire of responses, as well as the nature of the exquisite specificity that could be achieved, arguments abounded on the exact genetic mechanisms that enabled all these specificities to become part of the repertoire in every individual of the species.

Briefly, the arguments were as follows.

 By various calculations, the number of antigenic specificities toward which an immune response can be generated could range upward of 106–107.

 If every specific response, in the form of either antibodies or T‐cell receptors, were to be encoded by a single gene, did this mean that more than 107 genes (one for each specific antibody) would be required in every individual? How was this massive amount of DNA carried intact from individual to individual?

The pioneering studies of Susumu Tonegawa (1987 Nobel laureate) and Philip Leder, using molecular biological techniques, finally addressed these issues by describing a unique genetic mechanism by which B‐cell immunological receptors (BCRs) of enormous diversity could be produced with a modest amount of DNA reserved for this purpose.

The technique evolved by nature was one of genetic recombination in which a protein could be encoded by a DNA molecule composed of a set of recombined minigenes that made up a complete gene. Given small sets of these minigenes, which could be randomly combined to make the complete gene, it was possible to produce an enormous repertoire of specificities from a limited number of gene fragments. This is discussed in detail in Chapter 7.

Although this mechanism was first elucidated to explain the enormous diversity of antibodies that are not only released by B cells but that, in fact, constitute the antigen‐ or epitope‐specific receptors on B cells (BCRs), it was subsequently established that the same mechanisms operate in generating diversity of the antigen‐specific TCR. Mechanisms operating in generating diversity of BCRs and antibodies are discussed in Chapter 9. Those operating in generating diversity of TCRs are discussed in Chapter 10. Suffice it to say at this point that various techniques of molecular biology, that permit genes not only to be analyzed but also to be moved around at will from one cell to another, have continued to provide impetus to the onrushing tide of progress in the field of immunology.