Alt Named to Receive Paul Ehrlich and Ludwig Darmstaedter Prize

HMS researcher recognized for insights into antigen receptors

Frederick Alt, the HMS Charles A. Janeway Professor of Pediatrics at Boston Children’s Hospital, will be awarded the 2023 Paul Ehrlich and Ludwig Darmstaedter Prize, Germany’s highest medical award.

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Frederick Alt
Frederick Alt. Image: Paul Ehrlich Foundation

Alt and co-winner David Schatz of Yale Medical School will be recognized for their discovery of molecules and mechanisms that enable the immune system to recognize billions of different antigens.

“The picture we have today of the diversification of antigen receptors in the immune system of vertebrates is above all thanks to [Alt and Schatz],” said Thomas Boehm, chairman of the Scientific Council of the Paul Ehrlich Foundation.

“They have raised our knowledge of the development of the immune system to a new level,” Boehm said.

Antigen receptors — proteins capable of capturing antigens — come in two forms: antibodies produced by B cells and structures on the surface of T cells. The human body can build approximately 10 billion different antibodies but has genetic “blueprints” for only about 20,000 of these antibodies. The incredible variety of antibodies is made possible by a process of cutting up and reassembling the genetic information in DNA on certain chromosomes of maturing lymphocytes.

Schatz discovered the enzyme complex responsible for cutting the DNA, while Alt discovered the repair enzymes that join the cut segments. Additionally, Alt showed that this combinatorial diversity is increased by the insertion of very short, random DNA sequences, called N-nucleotides, at the interfaces of the gene segments to be joined.