The Journal of Immunology, Vol 148, Issue 3 746-752, Copyright © 1992 by American Association of Immunologists

ARTICLES

T cell receptor sequences from encephalitogenic T cells in adult Lewis rats suggest an early ontogenic origin

XM Zhang and E Heber-Katz
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.

In the Lewis rat, the encephalitogenic determinant of myelin basic protein (MBP), residues 68 to 88, induces an alpha beta + T cell population whose TCR beta-chains are exclusively derived from the V beta 8 TCR gene family. As presented here, sequencing of these beta- chains has revealed the following. 1) There is an absolute restriction to a single V beta 8 family member, previously identified as V beta 8.2. This V region is used by only 10% of the V beta 8+ TCR found in normal unprimed mesenteric and cervical lymph node T cell populations. 2) There is a serine at residue 97 (in the CDR3 region of the beta- chain) which appears to be Ag-specific and is not found in normal populations of adult T cells. 3) There is a size restriction of these MBP-specific beta-chains, resulting from the addition and deletion of nucleotides in the CDR3 region, which tend to cancel each other out. 4) There is a paucity of N-region nucleotide additions in the J region of these MBP-specific beta-chains. Such a reduced number of nontemplate- added nucleotides has been associated with receptors that rearrange early during development and fail to add nucleotides due to a lack of terminal deoxynucleotidyl transferase at that time. These results have led us to propose that the selection of MBP-reactive autoimmune T cells is based on both the Ag and the time frame when these cells are generated and enter the peripheral T cell pool.

This article has been cited by other articles:

				A. Junker, J. Ivanidze, J. Malotka, I. Eiglmeier, H. Lassmann, H. Wekerle, E. Meinl, R. Hohlfeld, and K. Dornmair Multiple sclerosis: T-cell receptor expression in distinct brain regions Brain, November 1, 2007; 130(11): 2789 - 2799. [Abstract] [Full Text] [PDF]

				M. Kreiss, A. Asmuss, K. Krejci, D. Lindemann, T. Miyoshi-Akiyama, T. Uchiyama, L. Rink, C. P. M. Broeren, and T. Herrmann Contrasting contributions of complementarity-determining region 2 and hypervariable region 4 of rat BV8S2+ (V{beta}8.2) TCR to the recognition of myelin basic protein and different types of bacterial superantigens Int. Immunol., May 1, 2004; 16(5): 655 - 663. [Abstract] [Full Text] [PDF]

				A. Miyakoshi, W. K. Yoon, Y. Jee, and Y. Matsumoto Characterization of the Antigen Specificity and TCR Repertoire, and TCR-Based DNA Vaccine Therapy in Myelin Basic Protein-Induced Autoimmune Encephalomyelitis in DA Rats J. Immunol., June 15, 2003; 170(12): 6371 - 6378. [Abstract] [Full Text] [PDF]

				Y. Matsumoto, W. K. Yoon, Y. Jee, K. Fujihara, T. Misu, S. Sato, I. Nakashima, and Y. Itoyama Complementarity-Determining Region 3 Spectratyping Analysis of the TCR Repertoire in Multiple Sclerosis J. Immunol., May 1, 2003; 170(9): 4846 - 4853. [Abstract] [Full Text] [PDF]

				F. J. Baker, M. Lee, Y.-h. Chien, and M. M. Davis Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice PNAS, July 9, 2002; 99(14): 9374 - 9379. [Abstract] [Full Text] [PDF]

				R. B. Fritz, X. Wang, and M.-L. Zhao Alterations in the Spinal Cord T Cell Repertoire During Relapsing Experimental Autoimmune Encephalomyelitis J. Immunol., June 15, 2000; 164(12): 6662 - 6668. [Abstract] [Full Text] [PDF]

				Y. Matsumoto, Y. Jee, and M. Sugisaki Successful TCR-Based Immunotherapy for Autoimmune Myocarditis with DNA Vaccines After Rapid Identification of Pathogenic TCR J. Immunol., February 15, 2000; 164(4): 2248 - 2254. [Abstract] [Full Text] [PDF]

				G. Kim, K. Kohyama, N. Tanuma, H. Arimito, and Y. Matsumoto Persistent Expression of Experimental Autoimmune Encephalomyelitis (EAE)-Specific V{beta}8.2 TCR Spectratype in the Central Nervous System of Rats with Chronic Relapsing EAE J. Immunol., December 15, 1998; 161(12): 6993 - 6998. [Abstract] [Full Text] [PDF]

				A. C. Buenafe, H. Offner, M. Machnicki, H. Elerding, K. Adlard, R. Jacobs, A. A. Vandenbark, and G. Adamus EAE TCR Motifs and Antigen Recognition in Myelin Basic Protein-Induced Anterior Uveitis in Lewis Rats J. Immunol., August 15, 1998; 161(4): 2052 - 2059. [Abstract] [Full Text] [PDF]

				R. Weissert, A. Svenningsson, A. Lobell, K. L. de Graaf, R. Andersson, and T. Olsson Molecular and Genetic Requirements for Preferential Recruitment of TCRBV8S2+ T Cells in Lewis Rat Experimental Autoimmune Encephalomyelitis J. Immunol., January 15, 1998; 160(2): 681 - 690. [Abstract] [Full Text] [PDF]

				G. Kim, N. Tanuma, T. Kojima, K. Kohyama, Y. Suzuki, Y. Kawazoe, and Y. Matsumoto CDR3 Size Spectratyping and Sequencing of Spectratype-Derived TCR of Spinal Cord T Cells in Autoimmune Encephalomyelitis J. Immunol., January 1, 1998; 160(1): 509 - 513. [Abstract] [Full Text] [PDF]

				H. Hanawa, T. Inomata, H. Sekikawa, T. Abo, M. Kodama, T. Izumi, and A. Shibata Analysis of Heart-Infiltrating T-Cell Clonotypes in Experimental Autoimmune Myocarditis in Rats Circ. Res., January 1, 1996; 78(1): 118 - 125. [Abstract] [Full Text]