Harald von Boehmer

Professor of Pathology, Harvard Medical School
Chief: Laboratory of Lymphocyte Biology
Dana-Farber Cancer Institute
44 Binney Street
Smith 736
Boston, MA 02115
Tel: 617-632-6880
Fax: 617-632-6881
email:Harald_von_Boehmer@dfci.harvard.edu
1 Instructors, 3 Postdoctoral Fellows, 1 Graduate Student

T lymphocyte biology

Past: The lab succeeded in T cell cloning and T cell receptor for antigen (TCR) transfer between clones thereby establishing the ab TCR as a molecule essential and sufficient for MHC-restricted antigen recognition. The knowledge facilitated the generation of TCR transgenic mice in which the principles of positive and negative selection (rescue from and induction of programmed cell death) of developing T cells as mechanisms of generating an effective and self-tolerant immune system were discovered. The TCR controlled checkpoints in development enable the system to adapt to self and match lineage commitment and TCR specificity. TCR transgenic mice were likewise essential in the discovery of the pre-TCR that controls allelic exclusion by feed back inhibition of TCRb rearrangement and is essential for the generation of a diverse TCR repertoire.

Presently we make use of various transgenic mice to define mechanisms of intra and extra-thymic generation of Foxp3–expressing regulatory T cells and study their role in controlling autoimmunity (type 1 diabetes), cancer and tissue transplantation. The knowledge obtained in transgenic mice is translated to wild-type mice, with the goal to specifically prevent unwanted immune reactions such as b cell destruction, allergy and transplant rejection.

With lineage fate mapping and single cell analysis we continue to address lineage fate decisions and lymphoma development in immature T cells.

Papers & Publications:

Von Boehmer, H. Positive and negative selection in Basel. Nat. Immunol.9, 571 (2008).

Marson,A., Kretschmer,K., Frampton, G.M., Jacobsen, E.S., Polansky, J., MacIsaac, K.D., Levine, S.S., Fraenkel, E., von Boehmer, H., Young, R.A. Foxpf3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445, 931 (2007).

Verginis P, McLaughlin KA, Wucherpfennig KW, von Boehmer H, Apostolou I. Induction of antigen-specific regulatory T cells in wild-type mice: visualization and targets of suppression. Proc Natl Acad Sci USA 4;105 (9),3479-84 (2008).

Egawa,T., Kreslavsky,T., Littman, D.R., and von Boehmer,H. Lineage diversion of T cell receptor transgenic thymocytes revealed by lineage fate mapping.PLoS ONE 3 e1512 (2008).

Kreslavsky,T., A.Garbe,A. Krueger,and Harald von Boehmer T-cell receptor-instructed ab versus gd lineage commitment revealed by single-cell analysis. J.Exp. Med. 205, 1173-1186 (2008).