1. T cell recognition of hapten. Anatomy of T cell receptor binding of a H-2kd-associated photoreactive peptide derivative.
- Author
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Kessler B, Michielin O, Blanchard CL, Apostolou I, Delarbre C, Gachelin G, Grégoire C, Malissen B, Cerottini JC, Wurm F, Karplus M, and Luescher IF
- Subjects
- Amino Acid Sequence, Cell Line, Models, Molecular, Molecular Sequence Data, Mutagenesis, Peptide Mapping, Peptides chemistry, Photoaffinity Labels, Receptors, Antigen, T-Cell genetics, T-Lymphocytes, Cytotoxic immunology, H-2 Antigens chemistry, Haptens immunology, Peptides immunology, Receptors, Antigen, T-Cell immunology, T-Lymphocytes immunology
- Abstract
To elucidate the structural basis of T cell recognition of hapten-modified antigenic peptides, we studied the interaction of the T1 T cell antigen receptor (TCR) with its ligand, the H-2Kd-bound Plasmodium berghei circumsporozoite peptide 252-260 (SYIPSAEKI) containing photoreactive 4-azidobenzoic acid (ABA) on P. berghei circumsporozoite Lys259. The photoaffinity-labeled TCR residue(s) were mapped as Tyr48 and/or Tyr50 of complementary determining region 2beta (CDR2beta). Other TCR-ligand contacts were identified by mutational analysis. Molecular modeling, based on crystallographic coordinates of closely related TCR and major histocompatibility complex I molecules, indicated that ABA binds strongly and specifically in a cavity between CDR3alpha and CDR2beta. We conclude that TCR expressing selective Vbeta and CDR3alpha sequences form a binding domain between CDR3alpha and CDR2beta that can accommodate nonpeptidic moieties conjugated at the C-terminal portion of peptides binding to major histocompatibility complex (MHC) encoded proteins.
- Published
- 1999
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