David A. Hafler

Center Neurologic Diseases
Brigham and Women's Hospital
77 Avenue Louis Pasteur
Boston MA 02115
Broad Institute, MIT
Tel: 617-525-5330
Fax: 617-525-5333
e-mail:dhafler@rics.bwh.harvard.edu
14 Postdoctoral Fellows

The lab of molecular immunology focuses on the understanding of human autoimmune diseases. We believe that the investigation of naturally occurring human diseases give insight into the basic processes of T cell regulation, in addition to providing fundamental understanding and development of new therapies for human diseases. The laboratory investigates the autoimmune and infectious diseases including multiple sclerosis, type I diabetes, HTLV-I induced diseases and Lyme Disease. The laboratory has defined immunodominant epitopes of autoantigens, and has developed new technologies to measure both functionality and frequency of autoreactive T cells. Recent investigations of the laboratory have included the definition of immunodominant epitopes of myelin basic protein and proteolipid protein, and definition of MHC binding characteristics; an examination of how altered peptide ligands of autoantigens can signal and induce differential cytokine secretion of autoreactive T cells; enumeration of a very high frequency of T cells in patients with multiple sclerosis showing a sensitvity to Fas mediated apoptosis, use of MHC class I and II tetramers to examine the frequency and functionality of microbial reactive T cells in patients; examination of regulatory T cells in human autoimmune disease, in particular examination of CD1d restricted invariant T cells in IDDM; and more recently, we have identified methods to examine human CD4+CD25+ regulatory T cells. A major effort has also been initiated to determine the genetic cause of MS in a collaborative effort with the Human Genome Center of the Broad Insititute.

Papers & Publications:

1. Ota K, Matsui M, Milford E, Mackin G, Wiener HL, Hafler DA. T cell recognition of an immunodominant myelin basic
   protein epitope in multiple sclerosis. Nature 346:183-187, 1990.
2. Baecher-Allan C, Brown JA, Freeman GJ, Hafler, DA. CD4+CD25hi regulatory cells in human peripheral blood. Journal Immunol, 167:1245-53. 2001.
3. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199:7;1-10 (2004).
4. Kent SC, Chen Y, Bregoli L, Clemmings SM, Kenyon NS, Ricordi C, Hering B, Hafler DA. Expanded pancreatic lymph nodes T cells from type 1 diabetics recognize insulin A1-15. Nature 435:224-228;(2005).
5. International Multiple Sclerosis Genetics Consortium. Novel Risk Alleles for Multiple Sclerosis Identified by a Whole Genome Association Study. N Engl J Med (2007) in press.