Helena Reijonen , Ph.D.
Affiliate Assistant Professor, Immunology

Research Assistant Member, Diabetes Program
Benaroya Research Institute
1201 Ninth Ave Seattle WA 98101
tel: 206-341 1343
fax: 206-223 7638 e-mail:
Email: reijonen@benaroyaresearch.org

Helena Reijonen received her PhD at the University of Turku in Finland in 1994. She did her post-doctoral training in Dr Gerald Nepom’s laboratory, and is currently research assistant member at Benaroya Research Institute.

The precise nature of the T lymphocyte response in Type 1 diabetes, and the regulation of this response, is one of the key barriers to a full understanding of autoimmune predisposition, disease progression and the rational design of T cell immunotherapy. The research projects in my laboratory aim at improving the understanding of the diversity of the immune cell repertoire responsible for the destruction or protection of insulin-producing beta cells.

The focus is on the following areas:

1. Identification of T lymphocytes that are relevant for the progression to Type 1 diabetes, and understanding the characteristics of these cells. Utilization of MHC class II tetramers makes it possible to probe the T lymphocyte compartment for analysis of specificity and frequency. This is the most important goal toward proper monitoring of the progression of autoimmunity in the individuals who are at risk but have not progressed to diabetes yet. Also, in clinical trials aiming at intervention or prevention of diabetes, accurate measures of changes in the T cell responses are needed to determine the effect of immunomodulatory therapies.

2. Subjects with disease-associated HLA molecules have potentially autoreactive T cells which display a range of avidities. Selective amplification of high avidity cells may lead to skewing of this spectrum toward autoimmunity allowing high avidity cells to become more predominant. Our research group has demonstrated that high avidity CD4+ T cells present in the peripheral blood of patients with Type 1 diabetes display restricted TcR usage. The next step is evaluating whether progression to diabetes is driven by expansion of these T cells, and further determining their phenotypic characteristics.

3. The risk to develop Type 1 diabetes is associated with the presence of certain MHC class II gene variants whereas some other MHC class II genes confer dominant protection. The studies of disease regulation will clarify the modifying role of protective MHC class II molecules, and explore the underlying mechanism of MHC mediated protection.

Selected publications:

Reijonen H, Elliott JF, van Endert P, Nepom G. Differential presentation of glutamic acid decarboxylase 65 (GAD65) T cell epitopes among HLA-DRB1*0401 positive individuals. J Immunol 1999(Aug 1); 163: 16674-1681

Reijonen H, Daniels TL, Lernmark A, Nepom GT. GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. Diabetes 2000; 49(10):1621-1626

Reijonen H, Novak EJ, Kochik S, Heninger A-K, Liu AW, Kwok WW, and Nepom GT. Detection of GAD65 specific T-cells by MHC Class II tetramers in Type 1 diabetes patients and at-risk subjects. Diabetes, 2002; 51:1375-1382

Nepom GT, Buckner JH, Novak EJ, Reichstetter S, Reijonen H, Gebe J, Wang R, Swanson E, Kwok WW. HLA class II tetramers: tools for direct analysis of antigen-specific CD4+ T cells. Arthritis Rheum 2002; 46(1):5-12

Buckner JH, Holzer U, Novak EJ, Reijonen H, Kwok WW, Nepom GT. Defining antigen-specific responses with human MHC class II tetramers. J Allergy Clin Immunol. 2002, 110:199-208

Reijonen H and Kwok WW. Use of HLA class II tetramers in tracking antigen-specific T-cells and mapping of T-cell epitopes. Methods 2003; 29(3):282-8

Gebe JA, Falk BA, Rock KA, Kochik SA, Heninger A-K, Reijonen H, Kwok WW and Nepom GT. MHC-peptide recognition by self-antigen specific CD4+ T-cells is a low avidity interaction. Eur J Immunol 2003; 33(5):1409-17

Reijonen H, Kwok WW and Nepom GT. Detection of CD4+ autoreactive T-cells in T1D using HLA class II tetramers. NYAS 6th IDS: Immunology in Diabetes II, Ann Ny Acad Sci 2003, 1005:82-87

Mallone R, Kochik SA, Laughlin EM, Gersuk VH, Reijonen H, Kwok WW, Nepom GT. Differential recognition and activation thresholds in human autoreactive GAD-specific T-cells. Diabetes 2004; 53(4): 971-7

Reijonen H, Heninger A-K, Laughlin EM, Kochik SA, Falk BA, Kwok WW, Greenbaum C and Nepom GT. GAD65 specific CD4+ T cells with high antigen avidity are prevalent in peripheral blood of Type 1 diabetes patients. Diabetes 2004, 53:1987-94

Gebe JA, Masewicz SA, Kochik SA, Reijonen H and Nepom GT. Inhibition of altered peptide ligand-mediated antagonism of human GAD65-responsive CD4+ T cells by non-antagonizable T cells. Eur J Immunol 2004; 34: 3337-3345

Reijonen H and Concannon P. Genetics of Type 1 Diabetes. In Joslin’s Diabetes Mellitus, New York, Lippincott, Williams & Wilkins, 2005, p. 355-370.

Mallone R, Kochik SA, Reijonen H, Carson B, Ziegler SF, Kwok W and Nepom GT. Functional avidity directs T-cell fate in autoreactive CD4+ T-cells. Blood 2005; 106:2798-2805

Öling V, Marttila J, Ilonen J, Kwok WW, Nepom GT, Knip M, Simell O and Reijonen H. GAD65- and Proinsulin-Specific CD4+ T-Cells Detected by MHC Class II Tetramers in Peripheral Blood of Type 1 Diabetes Patients and At-Risk Subjects. J Autoimmunity 2005, Nov; 25(3):235-43

Yang J, Danke NA, Berger D, Reichstetter S, Reijonen H, Greenbaum C, Pihoker C, James EA and Kwok WW. Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects. J Immunol 2006; 176(5):2781-9

Posted September 2006