The Journal of Immunology, Vol 152, Issue 4 1790-1801, Copyright © 1994 by American Association of Immunologists

ARTICLES

V beta 5+ T cell receptors skew toward OVA+H-2Kb recognition

SR Dillon, SC Jameson and PJ Fink
Department of Immunology, University of Washington, Seattle 98195.

T cells recognize a complex of peptide Ag bound within the groove of MHC-encoded molecules. Although many studies have attempted to correlate TCR gene expression with specificity for particular Ag/MHC combinations, it is still not clear exactly how the TCR physically interacts with its cognate ligand. We have analyzed transgenic mice that carry a rearranged gene encoding a V beta 5.2+ TCR beta-chain derived from the CD8+ CTL clone B3, which is specific for chicken OVA+H- 2Kb. Surprisingly, we have found that peripheral lymphocytes isolated from naive V beta 5.2 transgenic mice can generate a strong primary anti-OVA CTL response when stimulated in vitro with OVA+H-2b, whereas generation of even a weak anti-OVA response from nontransgenic littermates requires in vivo priming. This response is Ag specific, because the transgenic mice are unable to respond with or without priming to vesicular stomatitis virus, which contains a dominant epitope presented in the context of H-2Kb. The precursor frequency of OVA-specific CTL in unprimed V beta 5.2 transgenic mice is approximately 30-fold higher than that in nontransgenic littermate controls. Reverse transcription-PCR analyses demonstrate that OVA- specific CTL lines derived from unprimed V beta 5.2 transgenic mice express a variety of TCR V alpha elements, indicating that the transgenic anti-OVA response is not solely due to the reconstitution of the original B3 TCR. In fact, our data suggest that even a nontransgenic V beta 5+ TCR is intrinsically OVA specific. First, five separate OVA-specific oligoclonal CTL lines derived from individual nontransgenic mice demonstrate dramatic skewing toward expression of V beta 5.1+ or V beta 5.2+ TCR over the course of several in vitro stimulations. Second, sorting for V beta 5+CD8+ nontransgenic cells enriches for OVA-specific CTL. However, peptide antagonism experiments using mutant forms of the Kb-restricted OVA peptide reveal distinct differences between the recognition patterns of two individual OVA- specific CTL lines derived from unprimed V beta 5.2 transgenic mice. These experiments support the notion that a discrete portion of the responding TCR can heavily influence but not necessarily be solely sufficient for the recognition of a peptide Ag presented in the cleft of an MHC-encoded molecule.

This article has been cited by other articles:

				F. R. Santori, Z. Popmihajlov, V. P. Badovinac, C. Smith, S. Radoja, J. T. Harty, and S. Vukmanovic TCRbeta Chain That Forms Peptide-Independent Alloreactive TCR Transfers Reduced Reactivity with Irrelevant Peptide/MHC Complex J. Immunol., May 15, 2007; 178(10): 6109 - 6114. [Abstract] [Full Text] [PDF]

				A. M. Gallegos and M. J. Bevan Central Tolerance to Tissue-specific Antigens Mediated by Direct and Indirect Antigen Presentation J. Exp. Med., October 18, 2004; 200(8): 1039 - 1049. [Abstract] [Full Text] [PDF]

				C. Viret, O. Lantz, X. He, A. Bendelac, and C. A. Janeway Jr. A NK1.1+ Thymocyte-Derived TCR {beta}-Chain Transgene Promotes Positive Selection of Thymic NK1.1+ {alpha}{beta} T Cells J. Immunol., September 15, 2000; 165(6): 3004 - 3014. [Abstract] [Full Text] [PDF]

				P. Wong, A. W. Goldrath, and A. Y. Rudensky Competition for Specific Intrathymic Ligands Limits Positive Selection in a TCR Transgenic Model of CD4+ T Cell Development J. Immunol., June 15, 2000; 164(12): 6252 - 6259. [Abstract] [Full Text] [PDF]

				C. A. Blish, B. J. Gallay, G. L. Turk, K. M. Kline, W. Wheat, and P. J. Fink Chronic Modulation of the TCR Repertoire in the Lymphoid Periphery J. Immunol., March 15, 1999; 162(6): 3131 - 3140. [Abstract] [Full Text] [PDF]

				T. Yokosuka, K. Takase, M. Suzuki, Y. Nakagawa, S. Taki, H. Takahashi, T. Fujisawa, H. Arase, and T. Saito Predominant Role of T Cell Receptor (TCR)-{alpha} Chain in Forming Preimmune TCR Repertoire Revealed by Clonal TCR Reconstitution System J. Exp. Med., April 15, 2002; 195(8): 991 - 1001. [Abstract] [Full Text] [PDF]