Vβ5+ T cell receptors skew toward OVA + H-2Kb recognition

Stacey R. Dillon, Stephen C. Jameson, Pamela J. Fink

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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 Vβ5.2+ TCR β-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 Vβ5.2 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 Vβ5.2 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 Vβ5.2 transgenic mice express a variety of TCR Vα 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 Vβ5+ TCR is intrinsically OVA specific. First, five separate OVA-specific oligoclonal CTL lines derived from individual nontransgenic mice demonstrate dramatic skewing toward expression of Vβ5.1+ or Vβ5.2+ TCR over the course of several in vitro stimulations. Second, sorting for Vβ5+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 Vβ5.2 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.

Original languageEnglish (US)
Pages (from-to)1790-1801
Number of pages12
JournalJournal of Immunology
Volume152
Issue number4
StatePublished - Feb 15 1994

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