Biology Reference
In-Depth Information
substances newly synthesized in the laboratory and have never appeared in
our evolutionary past.
BEGINNING OF IMMUNOCHEMISTRY
It is thus extremely difficult for biochemists and molecular biologists to
isolate one of these antibodies out of million or billion different ones in our
blood, and try to characterize its properties. On the other hand, over one
hundred years ago in 1848, a physician, Dr. Bence Jones, noticed patients
suffering from a type of cancer, multiple myeloma, excreted a protein in
their urine. On heating the urine in slight acid solution, he saw the protein
precipitating out of solution at 56-64 0 . It would re-dissolve on boiling
(Kabat, 1976). That protein is now known as Bence Jones protein named
after the discoverer. Subsequently, it was also found that such patient had
large amounts of a specific myeloma protein in their blood, different from
patient to patient. It appears as a large peak on starch gel electrophoresis of
serum proteins, and can thus be purified. However, its function is not
known. These proteins are known as immunoglobulins. A graduate student
at Rockefeller University, Edelman (1959), discovered that on reducing the
disulfide bonds the myeloma protein from a multiple myeloma patient
consisted of two chains of polypeptides, one heavy and one light, based on
their molecular weights. The light one corresponded to the Bence Jones
protein in the urine of the same patient. In the same year, Porter (1959)
showed that rabbit antibodies could be digested by papain to give two
distinct fractions, one could still bind antigen while the other had no
antibody activity. The combination of these two important discoveries
provided biochemists and molecular biologists the handle to start the
investigation of the properties of antibodies.
We now know that multiple myeloma is a cancer of one of the antibody
producing cells, and immunoglobulin is a generalized term for antibodies.
Indeed, the disease process, multiple myeloma, has achieved the task of
isolating one of the million or billion antibodies from the rest. In 1965,
Hilschmann and Craig at Rockefeller University determined the amino acid
sequences of the first three Bence Jones proteins from three different
patients and opened up a new scientific field known as immunochemistry.
Even though the three proteins were not completely sequenced by them at
the time of the publication of their important paper, these sequences
subsequently became available as shown in Fig. 1-1. For conciseness, as
commonly used in any biochemistry or molecular biology textbook, the
single letter abbreviations for amino acid residues are used.
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