Definition of TCR recognition sites on Ld-tum- complexes.
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 V alpha CDR3 region, predicted to interact with peptide. However, in contrast to the majority of Ld peptide ligands 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 His 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.
Alexander-Miller
M
M
Department of Genetics, Washington University School of Medicine, St Louis, MO 63132.
Robinson
R A
RA
Smith
J D
JD
Gillanders
W E
WE
Harrison
L G
LG
Hansen
T H
TH
Connolly
J M
JM
Lee
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell; C070850:transplantation antigen P91A, mouse