Definition of TCR recognition sites on Ld-tum-complexes

Martha Alexander-miller, Ruth A. Robinson, Joseph D. Smith, William E. Gillanders, Lisa G. Harrison, Ted H. Hansen, Janet M. Connolly, David R. Lee

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The P911 variant of the P815 mastocytoma was shown by Lurquin et al. (Cell 58:293,1989) to elicit rapid tumor rejection in a syngeneic host. This rejection was mediated by Ld-restricted cytotoxic T lymphocytes (CTL) for which targets could be sensitized by the synthetic peptide designated tum- (P91A-.12-24). In a previous study, T cell clones specific for Ld-tum- complexes displayed very restricted TCR usage and a characteristic TCR motif in the Vα CDR3 region, predicted to interact with peptide. However, in contrast to the majority of Ld peptide Uganda that are nonamers, the tum- peptide is a 13-mer and its sequence does not fit the Ld binding motif. Thus, to define shorter versions of the tum- 13-mer and residues involved in TCR recognition, nonamer derivatives were synthesized and compared in several different binding and functional assays. From these comparisons, the peptide TQNHRALDL was found to be the optimal nonamer. CTL recognition of Ala-substituted analogues of this peptide indicated that the Hls and Arg residues at positions 4 and 5 are important for TCR contact We propose that these basic residues of the tum- peptide interact with the previously defined acidic residues in the CDR3 region of several TCR known to recognize Ld-tum- complexes.

Original languageEnglish
Pages (from-to)1699-1707
Number of pages9
JournalInternational Immunology
Volume6
Issue number11
DOIs
StatePublished - Nov 1994

Keywords

  • Anchor residues
  • Ligand binding
  • Major histocompatibility
  • TCR contact

Fingerprint

Dive into the research topics of 'Definition of TCR recognition sites on Ld-tum-complexes'. Together they form a unique fingerprint.

Cite this