Jack L. Strominger

Last updated
Jack L. Strominger
Born (1925-08-07) August 7, 1925 (age 99)
New York City, US
Alma mater Harvard University
Yale Medical School
Known for penicillin mechanism of action
Major histocompatibility complex
SpouseAnn
Children Andrew Strominger, Ethan Strominger and Paul Strominger
Awards John J. Abel Award (1960)
Pfizer Award in Enzyme Chemistry (formerly known as the Paul-Lewis Award in Enzyme Chemistry) (1962)
Selman A. Waksman Award in Microbiology (1968)
Rose Payne Award (1986)
Hoescht-Roussel Award, American Society for Microbiology Pasteur Medal in Gold (1990)
Albert Lasker Award for Basic Medical Research (1995)
Paul Ehrlich and Ludwig Darmstaedter Prize (1996)
Japan Prize (1999)
Scientific career
Fields Biochemistry and Immunology
Institutions Washington University School of Medicine
University of Wisconsin Medical School
American Academy of Arts and Sciences
Harvard University
United States National Academy of Sciences
Dana–Farber Cancer Institute
Harvard Medical School
American Philosophical Society
American Society of Biochemistry and Molecular Biology
American Association for the Advancement of Science
American Association of Immunologists
American Society for Microbiology
American Society for Pharmacology and Experimental Therapeutics
American Chemical Society
Doctoral students Timothy A. Springer
Hidde Ploegh
Matthew F. Mescher
David J. Waxman
Joel N. H. Stern
Brandy L. Houser
Leonardo M.R. Ferreira
Peter Cresswell

Jack Leonard Strominger (born August 7, 1925) [1] is the Higgins Professor of Biochemistry at Harvard University, specializing in the structure and function of human histocompatibility proteins and their role in disease. He won the Albert Lasker Award for Basic Medical Research in 1995. [2] [3]

Contents

Early life and education

Strominger was born in New York City. He was born one of three brothers to a dentist father. He graduated from Bayside High School. He studied at Harvard University and completed his degree in psychology in 1944. During World War II, he entered the Navy V-12 program as part of Harvard College. In March 1946, he was discharged from the Navy. He received his MD degree in 1948 from Yale Medical School. [4]

Career

After graduation he joined the faculty at the Washington University School of Medicine. There he obtained a fellowship in the Department of Pharmacology with Oliver H. Lowry. Afterwards, he completed his residency in medicine at the University of Chicago, where he met his wife Ann, who was a student. In 1951, during the Korean War the United States Navy called him back into service to be stationed at a hospital in Bangkok, Thailand. Strominger married, and together, the newlyweds went to Bangkok. But, after only two or three months, he was ordered by the United States Navy to leave Bangkok. The remainder of his appointment as a commissioned officer was at the National Institutes of Health (NIH) in Bethesda, Maryland under Sanford Rosenthal, chief of the Laboratory of Pharmacology in the National Institute of Arthritis and Metabolic Diseases. From work he had done in the Lowry laboratory and using work begun by James T. Park, Strominger began new work into the recently-purified-compound penicillin's antibiotic mechanism of action. Strominger left the NIH, and, after brief study at Carlsberg Laboratory and Cambridge University, returned to Washington University in St. Louis as an assistant professor of pharmacology. At Washington University in St. Louis, he discovered that uridine nucleotide that accumulated in the penicillin-treated bacterium staphylococcus aureus was a precursor of the bacterial cell wall.

Strominger joined the University of Wisconsin, Madison, as chairman of the department of pharmacology from 1964 to 1968. There, with Donald J. Tipper in 1965, he demonstrated the mechanism of action by which antibiotic penicillins kill bacteria by inhibiting the completion of the synthesis of structural components of bacterial cell walls known as peptidoglycans. Penicillins specifically inhibit the activity of enzymes that are needed for the cross-linking of peptidoglycans during the final step in cell wall biosynthesis. These antibiotics do this by binding to the group of enzymes known as Penicillin-binding proteins using a chemical structure found on penicillin molecules known as a β-lactam ring. β-lactam imitates the naturally occurring acyl-D-alanyl-D-alanine substrate for the enzymes. [5]

He joined the Harvard faculty in 1968 to work in the biochemistry and molecular biology department specializing in microbial biochemistry, with a small portion of his time being devoted to organ transplantation biology. Knowledge was scarce with respect to the mechanisms of allograft rejection. There was none for the transplantation antigens. Graft acceptance or rejection was only hinted at through previous knowledge of Blood type erythrocyte transfusion. In the mid-1960's, Allan Davies from the United Kingdom had discovered a number of the 3,6-dideoxyhexoses that could be utilized to distinguish bacterial surfaces. Davies speculated that the specificity of transplantation antigen might also be determined by cell surface arrangements of sugars. Later, Stan Nathenson worked with Davies to characterize transplantation antigens and discovered that they could be solubilized from the surfaces of cells by the protease papain. [6]

In 1974, Stominger became a member of the Dana–Farber Cancer Institute, a cancer treatment and research institution in Boston, Massachusetts, one of the clinical affiliates and research institutes of Harvard Medical School. [3] At that time, the institute's director was Emil Frei who had been a classmate with Strominger at Yale Medical School. There he worked on immunology involving Major histocompatibility complex (MHC) proteins and their interaction with viruses. The MHC is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell membrane-embedded external surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules. Together with X-ray diffraction protein crystallographer Don Wiley, Strominger (who supplied biological cell culture systems and proteins) solved the chemical structures and three-dimensional structures of several MHC proteins, and further, solved the three-dimensional structures of the chemical complexes of these proteins during their peptide substrate interactions. [2] Early work, elucidated the three-dimensional structures of the human class I MHC molecules of HLA-A2, HLA-A68, and HLA-B27. Ultimately, papain-solubilized fragments of the human class II MHC antigens HLA-DR1, HLA-DR2, HLA-DR3, HLA-DR4, HLA-DR7, and HLA-DR8 were purified from homozygous human B lymphoblastoid cell lines and crystals were grown for diffraction studies.

Awards

Strominger was the first recipient of the Selman A. Waksman Award in Microbiology in 1968. [7] In 1969, Strominger received the Golden Plate Award of the American Academy of Achievement. [8] Strominger was elected to the American Academy of Arts and Sciences in 1967. [9] He was elected to the National Academy of Sciences in 1970, and the National Institute of Medicine in 1975. [10] [11] He was elected to the American Philosophical Society in 1994. [12] In 1999, he received the Japan Prize. [1]

Personal life

Strominger married Ann in 1951. She died in 2017. Their children are physicist Andrew Strominger, [13] Ethan Strominger and Paul Strominger.

Related Research Articles

Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many unique HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism. T cells recognize foreign HLA molecules and trigger an immune response to destroy the foreign cells. Histocompatibility testing is most relevant for topics related to whole organ, tissue, or stem cell transplants, where the similarity or difference between the donor's HLA alleles and the recipient's triggers the immune system to reject the transplant. The wide variety of potential HLA alleles lead to unique combinations in individuals and make matching difficult.

<span class="mw-page-title-main">Major histocompatibility complex</span> Cell surface proteins, part of the acquired immune system

The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.

<span class="mw-page-title-main">Human leukocyte antigen</span> Genes on human chromosome 6

The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

<span class="mw-page-title-main">MHC class I</span> Protein of the immune system

MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called cytosolic or endogenous pathway.

<span class="mw-page-title-main">Beta-2 microglobulin</span> Component of MHC class I molecules

β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells. In humans, the β2 microglobulin protein is encoded by the B2M gene.

<span class="mw-page-title-main">Pamela Bjorkman</span> American biochemist

Pamela Jane Bjorkman NAS, AAAS is an American biochemist and molecular biologist. She is the David Baltimore Professor of Biology and Biological Engineering at the California Institute of Technology (Caltech). Her research centers on the study of the three-dimensional structures of proteins related to Class I MHC, or Major Histocompatibility Complex, proteins of the immune system, and proteins involved in the immune responses to viruses. Bjorkman's goal is to improve current therapeutic applications. Bjorkman is most well known as a pioneer in the field of structural biology.

<span class="mw-page-title-main">HLA-DR</span> Subclass of HLA-D antigens that consist of alpha and beta chains

HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR and peptide, generally between 9 and 30 amino acids in length, constitutes a ligand for the T-cell receptor (TCR). HLA were originally defined as cell surface antigens that mediate graft-versus-host disease. Identification of these antigens has led to greater success and longevity in organ transplant.

<span class="mw-page-title-main">HLA-DRA</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms.

<span class="mw-page-title-main">MHC class II</span> Protein of the immune system

MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, macrophages, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.

HLA-DP is a protein/peptide-antigen receptor and graft-versus-host disease antigen that is composed of 2 subunits, DPα and DPβ. DPα and DPβ are encoded by two loci, HLA-DPA1 and HLA-DPB1, that are found in the MHC Class II region in the Human Leukocyte Antigen complex on human chromosome 6 . Less is known about HLA-DP relative to HLA-DQ and HLA-DR but the sequencing of DP types and determination of more frequent haplotypes has progressed greatly within the last few years.

<span class="mw-page-title-main">HLA-A</span> Protein-coding gene in the species Homo sapiens

HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I transmembrane proteins. The others are HLA-B and HLA-C. The protein is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant HLA-A gene, and the β chain (β2-microglobulin) is an invariant β2 microglobulin molecule. The β2 microglobulin protein is encoded by the B2M gene, which is located at chromosome 15q21.1 in humans.

<span class="mw-page-title-main">KLRD1</span> Mammalian protein found in Homo sapiens

CD94, also known as killer cell lectin-like receptor subfamily D, member 1 (KLRD1) is a human gene.

<span class="mw-page-title-main">Minor histocompatibility antigen</span>

Minor histocompatibility antigen are peptides presented on the cellular surface of donated organs that are known to give an immunological response in some organ transplants. They cause problems of rejection less frequently than those of the major histocompatibility complex (MHC). Minor histocompatibility antigens (MiHAs) are diverse, short segments of proteins and are referred to as peptides. These peptides are normally around 9-12 amino acids in length and are bound to both the major histocompatibility complex (MHC) class I and class II proteins. Peptide sequences can differ among individuals and these differences arise from SNPs in the coding region of genes, gene deletions, frameshift mutations, or insertions. About a third of the characterized MiHAs come from the Y chromosome. Prior to becoming a short peptide sequence, the proteins expressed by these polymorphic or diverse genes need to be digested in the proteasome into shorter peptides. These endogenous or self peptides are then transported into the endoplasmic reticulum with a peptide transporter pump called TAP where they encounter and bind to the MHC class I molecule. This contrasts with MHC class II molecules's antigens which are peptides derived from phagocytosis/endocytosis and molecular degradation of non-self entities' proteins, usually by antigen-presenting cells. MiHA antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells.

<span class="mw-page-title-main">TAP1</span> Protein-coding gene in the species Homo sapiens

Transporter associated with antigen processing 1 (TAP1) is a protein that in humans is encoded by the TAP1 gene. A member of the ATP-binding cassette transporter family, it is also known as ABCB2.

<span class="mw-page-title-main">CD74</span> Mammalian protein found in humans

HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74, is a protein that in humans is encoded by the CD74 gene. The invariant chain is a polypeptide which plays a critical role in antigen presentation. It is involved in the formation and transport of MHC class II peptide complexes for the generation of CD4+ T cell responses. The cell surface form of the invariant chain is known as CD74. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF).

<span class="mw-page-title-main">HLA-DQA2</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DQ(6) alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leukocyte antigen system.

<span class="mw-page-title-main">TAP2</span> Protein-coding gene in the species Homo sapiens

TAP2 is a gene in humans that encodes the protein Antigen peptide transporter 2.

Human leukocyte antigens (HLA) began as a list of antigens identified as a result of transplant rejection. The antigens were initially identified by categorizing and performing massive statistical analyses on interactions between blood types. This process is based upon the principle of serotypes. HLA are not typical antigens, like those found on surface of infectious agents. HLAs are alloantigens, they vary from individual to individual as a result of genetic differences. An organ called the thymus is responsible for ensuring that any T-cells that attack self proteins are not allowed to live. In essence, every individual's immune system is tuned to the specific set of HLA and self proteins produced by that individual; where this goes awry is when tissues are transferred to another person. Since individuals almost always have different "banks" of HLAs, the immune system of the recipient recognizes the transplanted tissue as non-self and destroys the foreign tissue, leading to transplant rejection. It was through the realization of this that HLAs were discovered.

<span class="mw-page-title-main">Hidde Ploegh</span>

Hidde Lolke Ploegh is an immunologist at Boston Children's Hospital, known for his contributions in understanding antigen processing and the evasion of the immune system by viruses.

<span class="mw-page-title-main">Narinder Kumar Mehra</span> Indian immunologist (born 1949)

Narinder Kumar Mehra is an Indian immunologist, head of the department of transplant immunology and immunogenetics of the SRL Limited, Gurgaon. He is a former dean of research and holds the ICMR Dr. C.G. Pandit National Chair at AIIMS. An elected fellow of the International Medical Sciences Academy, The World Academy of Sciences, Indian National Science Academy and National Academy of Sciences, India, Mehra is known for his research on histocompatibility and immunogenetics. The Council of Scientific and Industrial Research, the apex agency of the Government of India for scientific research, awarded him the Shanti Swarup Bhatnagar Prize for Science and Technology, one of the highest Indian science awards for his contributions to Medical Sciences in 1992. He received the Chevalier of the National Order of Merit from François Mitterrand in 2003.

References

  1. 1 2 Dr. Jack L. Strominger. japanprize.jp
  2. 1 2 "Lasker Foundation – 1995 Basic Medical Research Award". Lasker Foundation. 1995. Retrieved 1 February 2010.
  3. 1 2 "Jack Leonard Strominger". The Complete Marquis Who's Who (R) Biographies. Marquis Who's Who LLC. 6 November 2009.
  4. ↑ Strominger, Jack L. (2006). "The Tortuous Journey of a Biochemist to Immunoland and What He Found There". Annual Review of Immunology. 24: 1–31. doi: 10.1146/annurev.immunol.24.021605.090703 . PMID   16551242.
  5. ↑ Tipper, D. J.; Strominger, J. L. (October 1, 1965). "Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine". Proceedings of the National Academy of Sciences. 54 (4): 1133–1141. Bibcode:1965PNAS...54.1133T. doi: 10.1073/pnas.54.4.1133 . PMC   219812 . PMID   5219821.
  6. ↑ Nathenson, S. G.; Davies, D. A. (1966). "Solubilization and partial purification of mouse histocompatibility antigens from a membranous lipoprotein fraction". Proceedings of the National Academy of Sciences of the United States of America. 56 (2): 476–483. Bibcode:1966PNAS...56..476N. doi: 10.1073/pnas.56.2.476 . PMC   224397 . PMID   5229968.
  7. ↑ "Selman A. Waksman Award in Microbiology". National Academy of Sciences. Archived from the original on 12 January 2011. Retrieved 15 February 2011.
  8. ↑ "Golden Plate Awardees of the American Academy of Achievement". www.achievement.org. American Academy of Achievement.
  9. ↑ "Jack Leonard Strominger". American Academy of Arts & Sciences. Retrieved 2022-02-10.
  10. ↑ "National Academy of Sciences: Directory Entry" . Retrieved 1 February 2010.
  11. ↑ "Institute of Medicine: Directory". Institute of Medicine, National Academy of Science. Archived from the original on 11 December 2012. Retrieved 1 February 2010.
  12. ↑ "APS Member History". search.amphilsoc.org. Retrieved 2022-02-10.
  13. ↑ "Still wrestling with big questions". Harvard News. 6 January 2020.

Further reading

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