Subject(s)
Histocompatibility Antigens Class I/history , NK Cell Lectin-Like Receptor Subfamily K/history , Receptors, Antigen, T-Cell, gamma-delta/history , Histocompatibility Antigens Class I/immunology , History, 20th Century , Humans , Killer Cells, Natural/immunology , Lymphocyte Activation/immunology , NK Cell Lectin-Like Receptor Subfamily K/immunology , T-Lymphocytes/immunologyABSTRACT
Hereditary hemochromatosis is caused by a potentially lethal recessive gene (HFE, C282Y allele) that increases iron absorption and reaches polymorphic levels in northern European populations. Because persons carrying the allele absorb iron more readily than do noncarriers, it has often been suggested that HFE is an adaptation to anemia. We hypothesize positive selection for HFE began during or after the European Neolithic with the adoption of an iron-deficient high-grain and dairying diet and consequent anemia, a finding confirmed in Neolithic and later European skeletons. HFE frequency compared with rate of lactase persistence in Eurasia yields a positive linear correlation coefficient of 0.86. We suggest this is just one of many mutations that became common after the adoption of agriculture.
Subject(s)
Adaptation, Biological/genetics , Hemochromatosis/genetics , Histocompatibility Antigens Class I/genetics , Membrane Proteins/genetics , White People/genetics , Anemia/genetics , Diet/history , Gene Frequency , Hemochromatosis/history , Hemochromatosis Protein , Histocompatibility Antigens Class I/history , History, Ancient , Humans , Membrane Proteins/history , White People/historyABSTRACT
Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism affecting about 1 in 250 individuals. HH results in an increased absorption of iron at the baso-lateral surface of the enterocyte with aberrant regulation of ferroportin-mediated transfer of iron in turn brought on by a decrease in circulating hepcidin. The medical literature describes a colorful history of HH with important contributions from faculty at Saint Louis University.
Subject(s)
Hemochromatosis/history , Histocompatibility Antigens Class I/history , Membrane Proteins/history , Hemochromatosis/genetics , Hemochromatosis/pathology , Hemochromatosis Protein , Histocompatibility Antigens Class I/genetics , History, 20th Century , Humans , Membrane Proteins/genetics , MissouriSubject(s)
Histocompatibility Antigens Class II/history , Histocompatibility Antigens Class I/history , Peptide Fragments/history , Receptors, Antigen, T-Cell/history , Animals , Antigen Presentation/immunology , Binding Sites/immunology , Histocompatibility Antigens Class I/chemistry , Histocompatibility Antigens Class I/metabolism , Histocompatibility Antigens Class II/chemistry , Histocompatibility Antigens Class II/metabolism , History, 20th Century , Humans , Mice , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Protein Binding/immunology , Receptors, Antigen, T-Cell/chemistry , Receptors, Antigen, T-Cell/metabolismSubject(s)
Antigen Presentation/genetics , Genes, MHC Class II/immunology , Histocompatibility Antigens Class II/history , Histocompatibility Antigens Class I/history , Signal Transduction/immunology , Amino Acid Sequence , Base Sequence , Biological Transport, Active/genetics , Biological Transport, Active/immunology , Cell Line, Transformed , History, 20th Century , Humans , Molecular Sequence Data , Signal Transduction/geneticsSubject(s)
Antigens, Viral/immunology , Histocompatibility Antigens Class I/chemistry , Histocompatibility Antigens Class I/immunology , Nucleoproteins/immunology , Peptides/immunology , RNA-Binding Proteins/immunology , Viral Core Proteins/immunology , Histocompatibility Antigens Class I/history , History, 20th Century , Membrane Proteins/metabolism , Nucleocapsid Proteins , Protein Binding , beta 2-Microglobulin/metabolismABSTRACT
My research career has focused on complex experimental systems, principally virus-induced infectious processes. I have always run my own experimental program and never had a major mentor, although I have had many great colleagues. After graduating from the School of Veterinary Science at the University of Queensland, Australia, I worked for nine years on diseases of domestic animals. During that interval I completed a part-time PhD at the University of Edinburgh while employed as an experimental neuropathologist. Returning to the John Curtin School of Medical Research in Canberra, I focused on cell-mediated immunity, started to work seriously with mice, and thus became both an immunologist and a basic medical scientist. It was there in 1973 that Rolf Zinkernagel and I discovered MHC I-restricted CD8(+) T cell recognition, a finding that, together with the "single T cell receptor/altered self" hypothesis that we developed to explain our results, led to the 1996 Nobel Prize for Physiology or Medicine. Part of my focus since then has been to communicate the societal value and power of science to the broader community. As my scientific life is not yet over, I confine the present historical account to the twentieth century.