Section: Research

Postdoctoral Position Available

Eric Huseby, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Pathology

Other Affiliation(s):
   Program in Immunology and Virology

Development of T cell tolerance of self and the autoimmune consequence of when it fails.

The major interest of my lab is to decipher how T cells develop tolerance to self proteins and the autoimmune  consequences of when tolerance fails.  The major route of establishing immunological tolerance of self occurs during the development of T cells in the thymus.  If the T cell receptor (TCR) on developing T cells (thymocytes) binds MHC + self peptides in the thymus with high affinity, the thymocyte is signaled to die.  However, if the TCR on the thymocyte binds MHC + self peptides within a range of medium affinity, T cells are signaled to live and enter the mature T cell repertoire. 

Most mature T cells, when activated, are pro-inflammatory in nature.  However, other T cells adopt an anti-inflammatory phenotype and function to turn off immune responses.  The signaling events which instruct whether thymocytes live or die and whether mature T cells are pro-inflammatory or anti-inflammatory originate from how the TCR binds MHC + self peptides during development in the thymus.  To identify how the biophysics of TCR binding MHC + peptides instructs thymocytes, we have measured the binding affinity and kinetics of binding for a series of TCRs binding several MHC + peptide combinations.  Using these TCR - MHC + peptide combinations, we are studying how different biophysical parameters influence the development T cells. 

Although thymic deletion purges most T cells with reactivity for self proteins, autoimmune diseases clearly demonstrate that T cell tolerance of self is incomplete. Many studies have indicated that everyone harbors T cells reactive to self proteins, however only a fraction of people succumb to autoimmune disease.  Thus not all self reactive T cell repertoires are pathogenic.  Using a T cell mediated model of the autoimmune disease multiple sclerosis, we are determining whether there is a T cell intrinsic difference in self-reactive, pathogenic versus non-pathogenic T cell repertoires or whether all self reactive T cell repertoires have the capability to pathogenic and  autoimmunity is predominately a reaction to a specific triggering event. 

Office: S2 122 & 123
Phone: 508-856-2180
E-mail: Eric.Huseby@umassmed.edu
Keywords: Immunology, Autoimmunity, T lymphocytes, Tolerance

More on Eric Huseby's Research Research | Publications | Rotations | Biography View All Sections on One Page

Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Huseby for additional details.