| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel; and
Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
The advent in recent years of the application of tetrameric arrays of class I peptide-MHC complexes now enables us to detect and study rare populations of Ag-specific CD8+ T cells. However, available methods cannot visualize or determine the number and distribution of these TCR ligands on individual cells nor detect APCs in tissues. In this study, we describe for the first time studies of human class I peptide-MHC ligand presentation. These studies were facilitated by applying novel tools in the form of peptide-specific, HLA-A2-restricted human recombinant Abs directed toward a viral epitope derived from human T cell lymphotropic virus type I. Using a large human Ab phage display library, we isolated a large panel of recombinant Fab Abs that are specific for a particular peptide-MHC class I complex in a peptide-dependent, MHC-restricted manner. We used these Abs to visualize the specific complex on APCs and virus-infected cells by flow cytometry, to quantify the number of, and visualize in situ, a particular complex on the surface of APCs bearing complexes formed by naturally occurring active intracellular processing of the cognate viral Ag. These findings demonstrate our ability to transform the unique fine specificity, but low intrinsic affinity of TCRs into high affinity soluble Ab molecules endowed with a TCR-like specificity toward human viral epitopes. These molecules may prove to be crucial useful tools for studying MHC class I Ag presentation in health and disease as well as for therapeutic purposes in cancer, infectious diseases, and autoimmune disorders.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  Y. Michaeli, G. Denkberg, K. Sinik, L. Lantzy, C. Chih-Sheng, C. Beauverd, T. Ziv, P. Romero, and Y. Reiter Expression Hierarchy of T Cell Epitopes from Melanoma Differentiation Antigens: Unexpected High Level Presentation of Tyrosinase-HLA-A2 Complexes Revealed by Peptide-Specific, MHC-Restricted, TCR-Like Antibodies J. Immunol., May 15, 2009; 182(10): 6328 - 6341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Klechevsky, M. Gallegos, G. Denkberg, K. Palucka, J. Banchereau, C. Cohen, and Y. Reiter Antitumor Activity of Immunotoxins with T-Cell Receptor-like Specificity against Human Melanoma Xenografts Cancer Res., August 1, 2008; 68(15): 6360 - 6367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zehn, C. J. Cohen, Y. Reiter, and P. Walden Efficiency of peptide presentation by dendritic cells compared with other cell types: implications for cross-priming Int. Immunol., December 1, 2006; 18(12): 1647 - 1654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhu, H. J. Belmont, S. Price-Schiavi, B. Liu, H.-i. Lee, M. Fernandez, R. L. Wong, J. Builes, P. R. Rhode, and H. C. Wong Visualization of p53264-272/HLA-A*0201 Complexes Naturally Presented on Tumor Cell Surface by a Multimeric Soluble Single-Chain T Cell Receptor. J. Immunol., March 1, 2006; 176(5): 3223 - 3232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Laugel, J. M. Boulter, N. Lissin, A. Vuidepot, Y. Li, E. Gostick, L. E. Crotty, D. C. Douek, J. Hemelaar, D. A. Price, et al. Design of Soluble Recombinant T Cell Receptors for Antigen Targeting and T Cell Inhibition J. Biol. Chem., January 21, 2005; 280(3): 1882 - 1892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamano, C. J. Cohen, N. Takenouchi, K. Yao, U. Tomaru, H.-C. Li, Y. Reiter, and S. Jacobson Increased Expression of Human T Lymphocyte Virus Type I (HTLV-I) Tax11-19 Peptide-Human Histocompatibility Leukocyte Antigen A*201 Complexes on CD4+ CD25+ T Cells Detected by Peptide-specific, Major Histocompatibility Complex-restricted Antibodies in Patients with HTLV-I-associated Neurologic Disease J. Exp. Med., May 17, 2004; 199(10): 1367 - 1377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Oh, M. Terabe, C. D. Pendleton, A. Bhattacharyya, T. K. Bera, M. Epel, Y. Reiter, J. Phillips, W. M. Linehan, C. Kasten-Sportes, et al. Human CTLs to Wild-Type and Enhanced Epitopes of a Novel Prostate and Breast Tumor-Associated Protein, TARP, Lyse Human Breast Cancer Cells Cancer Res., April 1, 2004; 64(7): 2610 - 2618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Biddison, R. V. Turner, S. J. Gagnon, A. Lev, C. J. Cohen, and Y. Reiter Tax and M1 Peptide/HLA-A2-Specific Fabs and T Cell Receptors Recognize Nonidentical Structural Features on Peptide/HLA-A2 Complexes J. Immunol., September 15, 2003; 171(6): 3064 - 3074. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
