T cell recognition of hapten. Anatomy of T cell receptor binding of a H-2kd-associated photoreactive peptide derivative

Kessler, B.Michielin, O.Blanchard, C. L.Apostolou, I.Delarbre, C.Gachelin, G.Gregoire, C.Malissen, B.Cerottini, J. C.Wurm, F.Karplus, M.Luescher, I. F.2007-06-052007-06-052007-06-05199910.1074/jbc.274.6.3622https://infoscience.epfl.ch/handle/20.500.14299/7666WOS:0000784282000519920911To 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.Amino Acid SequenceCell LineH-2 Antigens/*chemistryHaptens/*immunologyModelsMolecularMolecular Sequence DataMutagenesisPeptide MappingPeptides/chemistry/*immunologyPhotoaffinity LabelsReceptorsAntigenT-Cell/genetics/*immunologyT-Lymphocytes/*immunologyT-LymphocytesCytotoxic/immunologyT cell recognition of hapten. Anatomy of T cell receptor binding of a H-2kd-associated photoreactive peptide derivativetext::journal::journal article::research article