TY - JOUR
T1 - Definition of TCR recognition sites on Ld-tum-complexes
AU - Alexander-miller, Martha
AU - Robinson, Ruth A.
AU - Smith, Joseph D.
AU - Gillanders, William E.
AU - Harrison, Lisa G.
AU - Hansen, Ted H.
AU - Connolly, Janet M.
AU - Lee, David R.
N1 - Funding Information:
We are grateful to Nancy Myers for the fluorometric analyses shown in Fig. 6 and to Rita Piller for expert secretarial assistance. We also thank Drs Joyce Solheim, Beatriz Carreno and James Cook for critical review. This woxk was supported by National Institutes of Health Grants AI-31129 to D. R. L, AI-27568 to J. M. C. and AI-19687 to T. H. H.
PY - 1994/11
Y1 - 1994/11
N2 - 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.
AB - 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.
KW - Anchor residues
KW - Ligand binding
KW - Major histocompatibility
KW - TCR contact
UR - http://www.scopus.com/inward/record.url?scp=0028135168&partnerID=8YFLogxK
U2 - 10.1093/intimm/6.11.1699
DO - 10.1093/intimm/6.11.1699
M3 - Article
C2 - 7865463
AN - SCOPUS:0028135168
SN - 0953-8178
VL - 6
SP - 1699
EP - 1707
JO - International Immunology
JF - International Immunology
IS - 11
ER -