Tetramer Biomarker
Tetramer Information for Scientists
MHC “tetramers” are a multivalent synthetic mimic of the peptide binding proteins found on the surface of antigen presenting cells. Our tetramers are produced from soluble biotinylated Class II α a/b dimers conjugated around a fluorescent labeled streptavidin core. Class II tetramer reagents are a flow cytometry reagent that can be used to study human CD4+ T cell responses in a wide variety of disease settings. Because of the exquisite sensitivity and specificity of the MHC-peptide-TCR complex, tetramers can be used to individually label, enumerate, and sort T cells with one known antigen specificity.
The Benaroya Research Institute at Virginia Mason is pleased to distribute tetramer reagents for use by the scientific community through our Tetramer Core Laboratory. For specific guidelines for using these reagents, see the link below.
"Tetramer Methods & Staining Protocol used at BRI." (PDF, 692 KB)
Journal publications on MHC class II tetramers.
Click on the links to read the full version of the article:
Macaubas C, Wahlstrom J, Galva da Silva A, Forsthuber T, Sønderstrup G, Kwok WW, DeKruyff R, Umetsu D. Allergen-Specific MHC Class II Tetramer Cells Are Detectable in Allergic, but Not in Nonallergic, Individuals. (PDF, 397 KB) The Journal of Immunology, 176: 5069-5077, 2006.
Yang J, Danke N, Berger D, Reichstetter S, Reijonen H, Greenbaum C, Pihoker C, James W, Kwok WW. Islet-Specific Glucose-6-Phosphatase Catalytic Subunit-Related Protein-Reactive CD4+ T Cells in Human Subjects. (PDF, 653 KB) The Journal of Immunology, 176: 2781-2789, 2006.
Yang J, James E, Huston L, Danke N, Liu A, Kwok WW. Multiplex mapping of CD4 T cell epitopes using class II tetramers. (PDF, 1.11 MB) Clinical Immunology 120, 21-32, 2006.
Danke N, Yang J, Greenbaum C, Kwok WW. Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. (PDF, 782 KB) Journal of Autoimmunity, 25:303-311, 2005.
Öling V, Marttila J, Ilonen J, Kwok WW, Nepom GT, Knip M, Simell O, 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 (PDF, 417 KB) Journal of Autoimmunity, 25: 235-243, 2005.
Reijonen H, Mallone R, Heninger AK, Laughlin EM, Kochik SA, Falk B, Kwok WW, Greenbaum C, Nepom GT. GAD65-specific CD4+ T-cells with high antigen avidity are prevalent in peripheral blood of patients with type 1 diabetes. (PDF, 289 KB) Diabetes 53:1987-94, 2004.
Reijonen H, Kwok WW. Use of HLA class II tetramers in tracking antigen-specifc T cells and mapping T-cell epitopes. (PDF, 386 KB) Methods 29:282-288, 2003
Buckner JH, Holzer U, Novak EJ, Reijonen H, Kwok WW, Nepom GT. Defining antigen-specific responses with human MHC class II tetramers. (PDF, 867 KB) J. Allergy Clin. Immunol. 110:199-208, 2002.
Reijonen H, Novak E, Kochik S, Heninger A, Liu A, Kwok WW, Nepom GT. Detection of GAD65 specific T cells by MHC class II tetramers in type I diabetes patients and at-risk subjects. (PDF, 351 KB) Diabetes 51:1375-1382, 2002. "Reprinted with permission from Elsevier Science". Trends in Immunology & ScienceDirect©.
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. (PDF, 439 KB) Arthritis Rheum. 46:5-12, 2002.
Kwok WW, Gebe JA, Liu A, Agar S, Ptacek N, Hammer J, Koelle DM, Nepom GT. Rapid epitope identification from complex class-II restricted T-cell antigens. (PDF, 133 KB) Trends Immunol. 22:583-588, 2001
Novak, EJ, Masewicz, SA, Liu, AW, Lernmark, A, Kwok, WW, and Nepom, GT. Activated human epitope-specific T cells identified by class II tetramers reside within a CD4high, proliferating subset. (PDF, 471 KB) Int. Immunol. 13:799-806, 2001
Novak, EJ, Liu, AW, Gebe, JA, Falk, B, Nepom, GT, Koelle, DM and Kwok, WW. Tetramer-guided epitope mapping: rapid identification and characterization of immunodominant CD4+ T cell epitopes from complex antigens. (PDF, 1.8 MB) J. Immunol. 166:6665-6670, 2001
Kwok, WW, Liu, AW, Novak, EJ, Gebe, JA, Ettinger, RA, Nepom, GT, Reynolds, S, and Koelle, D. HLA-DQ tetramers identify epitope-specific T cells in peripheral blood of herpes simplex virus type-2-infected individuals: direct detection of immunodominant antigen-responsive cells. (PDF, 83 KB) J. Immunol. 164:4244-4249, 2000
Reichstetter, S, Ettinger, RA, Liu, AW, Gebe, JA, Nepom, GT and Kwok, WW. Distinct T cell interactions with HLA class II tetramers characterize a spectrum of TCR affinities in the human antigen-specific T-cell response.(PDF, 401 KB) J. Immunol. 165:6994-6998, 2000
Novak, EJ, Liu, AW, Nepom, GT, and Kwok, WW. MHC Class II tetramers permit detection and characterization of peptide-specific human CD4+ T cells proliferating to influenza A antigen. (PDF, 221 KB) J.Clin.Invest. 104:R63-R67, 1999