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Antibody Structure, Function and Genetics

“What a memorable day! The Pneumococcal reactants were most exciting—sugarplums were dancing in my head.”

  • —Michael Potter, “The Early History of Plasma Cell Tumors in Mice, 1954–1976.”

Matching Immunoglobulins to their Antigens

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To study the structure and function of antibodies or immunoglobulins, Potter had to determine which antigens they reacted with. Serendipity struck when Myron Leon from St. Luke’s Hospital in Cleveland came for a one-day visit in October 1967, bringing several antigens he wanted to screen. Potter offered his myeloma serum samples, containing a mix of plasma cell tumors and antibodies. The Ouchterlony plates were prepared mixing Leon’s antigens with Potter’s serum, and they went out to dinner to await the reactions. The result, shown to the right, revealed an immunoglobulin reacting to a specific antigen associated with pneumococcus bacteria, a breakthrough revelation.

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this data depicts the structure of Immunoglobulin and had labels for 8 pm lb 15 and 603

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Potter and Leon's Ouchterlony Plate (1967)

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National Library of Medicine


Potter and Mushinski standing in the lab

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In their Building 8 laboratory, Potter and Elizabeth Mushinski began screening the immunoglobulins produced by plasma cell tumors against all types of antigens to match antibody to antigen. In 1968, they identified the MOPC315 immunoglobulin and its antigen, pneumococcal C polysaccharide, which is a component of the bacteria that causes pneumonia.

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Michael P. Cancro, Ph.D., University of Pennsylvania


What Makes Immunoglobulins Differ Genetically?

potters handwritten notes transcribed on page

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  1. Why do BALB/c mice get plasma cell tumors and most other strains do not?
  2. Are the antigens mouse myeloma proteins bind related to immunogenesis?
  3. What is the genetic basis of antibody diversity?


Potter worked with Rose Lieberman on the third question he had scrawled: What is the genetic basis of antibody diversity? They found three genetic “types” in each immunoglobulin. “Isotype” genes on the constant regions determine the class and sub-class of the immunoglobulin. “Allotypes” distinguish the constant region sequences that are unique to the mouse strain. And “idiotypes” in the variable region reflect genetic sequences associated with an immunoglobulin’s specificity; sometimes immunoglobulins bind to the same antigen, but their idiotype genes are different.


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The illustration, on the right, shows the basic structure of immunoglobulins. Molecules in the heavy chains weigh more than those in the light chains. The amino acids in the constant regions do not change, while those in the variable region usually do change. Potter asked how this structure affects how immunoglobulins protect the body.

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Graphic depicting antigen binding sites

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Based on an illustration from the University of Arizona


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This 1976 photograph shows how Potter augmented his glasses with the addition of magnifying lenses that allowed him to see small details. It is perhaps the best visual metaphor for his careful and precise research.

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Michael P. Cancro, Ph.D., University of Pennsylvania
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