Jan Klein
Jan Klein was a Czech–American immunologist.
Professional life
Jan Klein was a Czech-American immunologist, best known for his work on the major histocompatibility complex. He was born in 1936 in Stemplovec, Opava, Czech Republic. He graduated from the Charles University at Prague, in 1955, and received his M.S. in botany from the same school in 1958. He was a teacher at the Neruda High School in Prague from 1958 to 1961. He received his Ph.D. in genetics from the Czechoslovak Academy of Sciences in 1965, and moved to Stanford University as a postdoctoral fellow in 1968. He became assistant professor in 1969, and associate professor in 1973 at the University of Michigan. He assumed the position of professor at the University of Texas Southwestern Medical School in 1975. From 1977 to his retirement in 2004, he was the director of the Max-Planck-Institut für Biologie at Tübingen, Germany. From 2004 to his death in 2023, he was a Frances R. and Helen M. Pentz Visiting Professor of Science and adjunct professor of biology at the Pennsylvania State University.Research interests
Klein's scientific output encompasses 600 publications in scientific journals and a dozen of books, which he either authored or edited. It spans three major disciplines: genetics, immunology, and evolutionary biology, as well as one interface discipline: immunogenetics. His major research focus was on the major histocompatibility complex,, which comprises series of genes, which play a critical part in the initiation of the adaptive immune response, exemplified by the production of antibodies specific for different pathogens.Major accomplishments
Redefinition of Immunology
In his textbooks and other writings, Klein introduced a new concept of immunology, in which he conceived the discipline as a branch of biological sciences, rather than as a narrow province of medical studies, as it had been represented traditionally. He defined immunology as the science of self-nonself discrimination, concerned not just with the human species and its animal models, but with all organisms; and not just with issues of human health, but with normal physiological functions, executed with specialized body systems. He was the first to include in an immunology textbook sections emphasizing the importance of the so-called non-adaptive immune system. He also gave immunology a logical internal structure. Instead of organizing his textbooks into sections such as immunochemistry, immunobiology, immunogenetics, immunopathology, and so on, as was then customary, he presented it as a self-contained science. He organized it as a science operating with specialized organs, cells, genes, molecules, mechanisms, phenotypes, and functions.Redefinition of Immunogenetics
In his experimental work, his 25 years as a director of the Immunogenetics Division of the , and nearly the same period of time at the helm of the journal , Klein strived to redefine the immunogenetics discipline. Immunogenetics emerged in the 1930s as the study of genes controlling antigens detected by antibodies. This was a very artificial delineation of a discipline, based essentially on a method, rather than on an internal content. In Klein's conception, immunogenetics was to deal with what immunology and genetics have in common—a set of genes that control and effect immune responses of any kind.Discovery of Class II Genes and the Concept of Mhc
In the adaptive immune system, the three preeminent sets of genes are those that code for the Mhc, T-cell receptor, and B-cell receptor proteins. Klein contributed to the study of all three systems, but his primary interest was in the Mhc system. He developed the modern concept of the Mhc as consisting of two principal kinds of gene, for which he coined the designations class I and class II genes. The class I genes were discovered in 1936 as coding for blood group antigens, which, however, were also responsible for the rejection of incompatible grafts. Klein, with his coworker Vera Hauptfeld and his wife Dagmar Klein, were the first to describe the product of the class II genes and identify them as the molecules that control level of antibodies synthesized in response to foreign antigens. Earlier, Hugh O. McDevitt and his coworkers mapped an Immune response-1 locus influencing the level of antibody production against the synthetic polypeptide -L—A into the Mhc. Klein and his coworkers, finding their locus inseparable from the postulated Ir-1 locus, concluded that the class II antigens they demonstrated on the surfaces of lymphocytes were the product of the Ir-1 locus. Later studies confirmed this interpretation. Genetic mapping of the loci controlling the class I and class II antigens of the mouse showed them to be part of a cluster, which Klein mapped to the chromosome 17 and for which he championed the name major histocompatibility locus, Mhc. The name referred to the fact that the genes were part of a set that controlled tissue compatibility and in this set one cluster had the strongest effect. George D. Snell named the tissue compatibility genes histocompatibility 1, 2, 3, etc., in the order of discovery, and since the H2 genes happened to be strongest of the set, they became the first Mhc known. All other histocompatibility genes came to be called minor.Initially, genetic mapping of the mouse class I antigens suggested the existence of multiple class I loci in the H2 complex. Soon, however, inconsistencies in the assignment of certain antigens to loci signaled that something was amiss with the H2 maps, as they were then drawn. Klein and Donald C. Shreffler solved the problem by demonstrating that a given antigen could be present on molecules controlled by different loci. Taking this finding into account, they were able to reduce the number of the class I loci to two, H2K and H2D. This "two-locus model" played a n important part in subsequent interpretations of the Mhc. The model was also consistent with the results of earlier Klein's PhD work, in which he discovered that immune selection for a loss of certain H2 antigens on somatic cells was accompanied by the loss of some but not other unselected antigens. In this respect, the antigens fell into two groups as if carried by two different molecules. The discovery of the class II genes had been fitted into the model by the demonstration that they mapped between the H2K and the H2D. Shreffler also demonstrated the existence of another locus mapping between the two class I loci. It coded for what he called the "serum serological" or Ss protein, present in a soluble form in the blood fluid phase, in contrast to the class I and class II antigens, which were expressed on cell surfaces. At that stage, the H2 complex could be divided into four regions: class I...Class II...Ss...Class I.
These developments alerted immunologists on the one hand and transplantation biologists on the other of the Mhc’s potential importance for their respective disciplines. The consequence was a proliferation of reports describing association of a variety of phenomena with the complex. The associations were demonstrated by testing the responses of congenic strains differing at the H2 complex and mapping the genes controlling the responses within the H2 complex with the help of strains carrying H2 haplotypes derived by intra-H2 recombinations. These strains were developed by George D. Snell, Jack H. Stimpfling, Donald C. Shreffler, and Jan Klein. The phenomena included control of antibody response to a variety of antigens, both natural and synthetic; suppression of immune response by special suppressor cells or soluble factors; proliferation of lymphocytes in an in vitro culture challenged with H2-incompatible stimulating cell ; killing of H2-icompatible target cells by sensitized lymphocytes ; response of transplanted immune cell against the tissues of the host ; rejection of H2-incompatible grafts by the recipients; and others. All these phenomena appeared to be controlled by different loci within the Mhc. As a result, the H2 complex appeared to expand by the addition of new loci. Klein's group, however, challenged this interpretation and in a series of carefully controlled studies demonstrated that the new loci were in reality mirages generated by various forms of interaction involving the established class I and class II loci. In this manner, Klein contracted the H2 complex back to the version established by the serological methods, and propounded the view that the various responses were controlled by the class I and class II loci, rather than by separate loci. Later, other loci were again mapped within the H2 complex and these were no phantoms. They were real but, as Klein argued, they were unrelated to the class I and class II loci and ended up in the region by chance. The general opinion was, however, that they represented the class III region of the Mhc, that they were functionally related to the Mhc by being involved in immune response, and that the complex functioned as an immune supergene. The first of these class III loci was the Ss locus, which was later identified as coding for complement component 4. The C4 protein was indeed involved in immunity by being one in a series of protein molecules that attach to a cell-bound antibody to puncture a hole in it and thus kill it. But nobody could come up with a reason why it had to be linked to the class I or class II genes to function properly. Similar arguments could be applied to the other class III genes. Later, Klein's view received a strong support when his group discovered that in the fishes, which comprise more than half of jawed vertebrates, not even the class I and class II genes were in a single cluster and the class III genes were scattered all over the genome. Ultimately, the modern concept prevailed against the tendencies to make the Mhc unnecessarily nonparsimonious.