Harald von Boehmer

Harald von Boehmer (30 November 1942 – 24 June 2018) was a German-Swiss immunologist and author best known for his work on T cells.

Career The youngest of Hasso von Boehmer's three children, von Boehmer obtained an M.D. from LMU Munich (1968) and a Ph.D. from Melbourne University, Australia (1974). He was a member of the Basel Institute for Immunology in Switzerland (1973–1996), director of Unité INSERM 373 at the René Descartes University in Paris, France and is Professor of Pathology at Harvard Medical School and the Faculty of Arts and Sciences of Harvard University, Cambridge and Chief of the Laboratory for Lymphocyte Biology at the Dana Farber Cancer Institute in Boston. He was an adjunct professor at the University of Florida.

Von Boehmer studied the role of T lymphocytes in the immune system. In particular, he addressed the contribution of the T cell receptor (TCR) to recognition by T cells of peptide-MHC complexes by transfer of TCR alpha and beta genes from one T cell clone to another. Questions concerned with the role of positive and negative selection of developing T cells by peptide-MHC complexes in the thymus in generating an effective and self-tolerant immune system were analyzed in TCR transgenic mice. The same experimental system served the purpose to study the impact of TCR-ligation on developing T cells by MHC class I and MHC class II ligands on the intrathymic generation of CD8 killer and CD4 helper cells, respectively. Further studies were concerned with the structure and function of the pre-T cell receptor and its role in controlling survival and differentiation of developing T cells that have succeeded in productive TCR beta rearrangement. Harald von Boehmer studied the generation and function of regulatory T cells that have an essential role in preventing autoimmunity with the goal to exploit these cells in the prevention of and interference with unwanted immune reactions.

Harald von Boehmer was elected as a Senior Member of the Institut Universitaire de France (1997), was awarded the Louis-Jeantet Prize for Medicine jointly with Nicole Le Douarin and Gottfried Schatz in Geneva (1990) and received an honorary Medical Degree from the University of Technology, Munich (2002).

Harald von Boehmer retired at the end of 2012 and was a guest professor at the Institute for Immunology of LMU Munich beginning January 2013.

In February 2013 Harald von Boehmer, MD, PhD, Professor of Microbiology and Immunology at the Department of Cancer Immunology & AIDS, Harvard Medical School (USA), did receive the Helmholtz International Fellow Award for having excelled in the field of Immunology.

Von Boehmer died on June 24, 2018, at the age of 75.

Awards 1990 Louis Jeantet Prize for Medicine (Geneva) 1990 Elected member of the Academia Europaea (London) 1990 Avery-Landsteiner-Prize of the German society for immunology (Aachen) 1993 Paul Ehrlich and Ludwig Darmstaedter Prize (Frankfurt) 1997 Körber European Science Prize (Hamburg) 1997 Elected member of the Institut Universitaire de France 2002 Honorary doctor in Medical degree of the Technical University of Munich 2003 Elected member of the German Academy of Sciences Leopoldina (Halle) 2003 National Institutes of Health NIH Merit Award (Washington D.C.) 2004 Sherman Fairchild Foundation award 2013 Helmholtz International Fellow Award

Selected publications Selected papers:

Bone marrow chimeras and transplantation tolerance von Boehmer, H.; Sprent, J.; Nabholz, M. (1975). "Tolerance to histocompatibility determinants in tetraparental bone marrow chimeras." Journal of Experimental Medicine. 141 (2): 322–334. . . This work contributed to the development of allogeneic bone marrow transplantation strategies using T-cell removal.

MHC restriction and T-cell recognition von Boehmer, H.; Hudson, L.; Sprent, J. (1975). "Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras." Journal of Experimental Medicine. 142 (4): 989–997. . . von Boehmer, H.; Haas, W. (1976). "Cytotoxic T lymphocytes recognize allogeneic tolerated, TNP-conjugated cells." Nature. 261: 141–143. These studies helped define how T cells recognize antigens in the context of MHC molecules.

T-cell receptor specificity Dembić, Z.; Haas, W.; Weiss, S.; McCubrey, J.; Kiefer, H.; von Boehmer, H.; Steinmetz, M. (1986). "Transfer of specificity by murine alpha and beta T-cell receptor genes." Nature. 320 (6059): 232–238. . . This paper showed that alpha and beta T-cell receptor genes could transfer antigen specificity.

Central tolerance and thymocyte deletion Kisielow, P.; Blüthmann, H.; Staerz, U. D.; Steinmetz, M.; von Boehmer, H. (1988). "Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes." Nature. 333 (6175): 742–746. . Swat, W.; Ignatowicz, L.; von Boehmer, H.; Kisielow, P. (1991). "Clonal deletion of immature CD4+8+ thymocytes in suspension culture by extrathymic antigen-presenting cells." Nature. 351: 150–153. . . These studies demonstrated central tolerance through deletion of immature T cells in T-cell receptor transgenic systems.

Positive selection and CD4/CD8 lineage choice Teh, H. S.; Kisielow, P.; Scott, B.; Kishi, H.; Uematsu, Y.; Blüthmann, H.; von Boehmer, H. (1988). "Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells." Nature. 335 (6187): 229–233. . . Scott, B.; Blüthmann, H.; Teh, H. S.; von Boehmer, H. (1989). "The generation of mature T cells requires interaction of the alpha beta T-cell receptor with major histocompatibility antigens." Nature. 338 (6216): 591–593. . . These studies helped establish the role of T-cell receptor interactions with MHC molecules in positive selection and CD4/CD8 lineage determination.

Peripheral selection of the T-cell repertoire Rocha, B.; von Boehmer, H. (1991). "Peripheral selection of the T cell repertoire." Science. 251 (4998): 1225–1228. . . This paper addressed peripheral tolerance through deletion and reversible anergy in mature T cells.

T-cell receptor allelic exclusion Borgulya, P.; Kishi, H.; Uematsu, Y.; von Boehmer, H. (1992). "Exclusion and inclusion of alpha and beta T cell receptor alleles." Cell. 69 (3): 529–537. . . Aifantis, I.; Buer, J.; von Boehmer, H.; Azogui, O. (1997). "Essential role of the pre-T cell receptor in allelic exclusion of the T cell receptor beta locus." Immunity. 7 (5): 601–607. . . These papers examined allelic exclusion at the T-cell receptor loci, including the role of the pre-T-cell receptor in TCR-beta allelic exclusion.

T-cell memory Bruno, L.; Kirberg, J.; von Boehmer, H. (1995). "On the cellular basis of immunological T cell memory." Immunity. 2 (1): 37–43. . . This study characterized memory T cells as phenotypically and functionally distinct from naive T cells.

Discovery and function of the pre-T-cell receptor Groettrup, M.; Ungewiss, K.; Azogui, O.; Palacios, R.; Owen, M. J.; Hayday, A. C.; von Boehmer, H. (1993). "A novel disulfide-linked heterodimer on pre-T cells consists of the T cell receptor beta chain and a 33 kd glycoprotein." Cell. 75 (2): 283–294. . . Saint-Ruf, C.; Ungewiss, K.; Groettrup, M.; Bruno, L.; Fehling, H. J.; von Boehmer, H. (1994). "Analysis and expression of a cloned pre-T cell receptor gene." Science. 266 (5188): 1208–1212. . . Fehling, H. J.; Krotkova, A.; Saint-Ruf, C.; von Boehmer, H. (1995). "Crucial role of the pre-T-cell receptor alpha gene in development of alpha beta but not gamma delta T cells." Nature. 375: 795–798. . . These studies identified, cloned, and tested the developmental role of the pre-T-cell receptor.

Regulatory T cells and Foxp3 Apostolou, I.; Sarukhan, A.; Klein, L.; von Boehmer, H. (2002). "Origin of regulatory T cells with known specificity for antigen." Nature Immunology. 3 (8): 756–763. . . Kretschmer, K.; Apostolou, I.; Hawiger, D.; Khazaie, K.; Nussenzweig, M. C.; von Boehmer, H. (2005). "Inducing and expanding regulatory T cell populations by foreign antigen." Nature Immunology. 6 (12): 1219–1227. . . Marson, A.; Kretschmer, K.; Frampton, G. M.; Jacobsen, E. S.; Polansky, J. K.; MacIsaac, K. D.; Levine, S. S.; Fraenkel, E.; von Boehmer, H.; Young, R. A. (2007). "Foxp3 occupancy and regulation of key target genes during T-cell stimulation." Nature. 445: 931–935. . . These papers addressed antigen-dependent generation of regulatory T cells and Foxp3-dependent gene regulation.