TY - JOUR
T1 - Differential roles of T cell receptor α and β chains in ligand binding among H-2K(d)-restricted cytolytic T lymphocyte clones specific for a photoreactive Plasmodium berghei circumsporozoite peptide derivative
AU - Anjuère, Fabienne
AU - Kuznetsov, Dmitry
AU - Romero, Pedro
AU - Cerottini, Jean Charles
AU - Jongeneel, C. Victor
AU - Luescher, Immanuel F.
N1 - Funding Information:
The first author is grateful to Fundacao para a Ciencia e Tecnologia (FCT) for the partial financing of the work under the Research and Development Unit for Mechanical and Industrial Engineering (UNIDEMI) Strategic Project UID/EMS/00667/2013 and SFRH/BPD/111787/2015.
PY - 1997/3/28
Y1 - 1997/3/28
N2 - To study the interaction of T cell receptor with its ligand, a complex of a major histocompatibility complex molecule and a peptide, we derived H- 2K(d)-restricted cytolytic T lymphocyte clones from mice immunized with a Plasmodium berghei circumsporozoite peptide (PbCS) 252-260 (SYIPSAEKI) derivative containing photoreactive N(ε)-[4-azidobenzoyl] lysine in place of Pro-255. This residue and Lys-259 were essential parts of the epitope recognized by these clones. Most of the clones expressed BV1S1A1 encoded β chains along with specific complementary determining region (CDR) 3β regions but diverse α chain sequences. Surprisingly, all T cell receptors were preferentially photoaffinity labeled on the chain. For a representative T cell receptor, the photoaffinity labeled site was located in the Vα C- strand. Computer modeling suggested the presence of a hydrophobic pocket, which is formed by parts of the Vα/Jα C-, F-, and G-strands and adjacent CDR3α residues and structured to be able to avidly bind the photoreactive ligand side chain. We previously found that a T cell receptor specific for a PbCS peptide derivative containing this photoreactive side chain in position 259 similarly used a hydrophobic pocket located between the junctional CDR3 loops. We propose that this nonpolar domain in these locations allow T cell receptors to avidly and specifically bind epitopes containing non-peptidic side chains.
AB - To study the interaction of T cell receptor with its ligand, a complex of a major histocompatibility complex molecule and a peptide, we derived H- 2K(d)-restricted cytolytic T lymphocyte clones from mice immunized with a Plasmodium berghei circumsporozoite peptide (PbCS) 252-260 (SYIPSAEKI) derivative containing photoreactive N(ε)-[4-azidobenzoyl] lysine in place of Pro-255. This residue and Lys-259 were essential parts of the epitope recognized by these clones. Most of the clones expressed BV1S1A1 encoded β chains along with specific complementary determining region (CDR) 3β regions but diverse α chain sequences. Surprisingly, all T cell receptors were preferentially photoaffinity labeled on the chain. For a representative T cell receptor, the photoaffinity labeled site was located in the Vα C- strand. Computer modeling suggested the presence of a hydrophobic pocket, which is formed by parts of the Vα/Jα C-, F-, and G-strands and adjacent CDR3α residues and structured to be able to avidly bind the photoreactive ligand side chain. We previously found that a T cell receptor specific for a PbCS peptide derivative containing this photoreactive side chain in position 259 similarly used a hydrophobic pocket located between the junctional CDR3 loops. We propose that this nonpolar domain in these locations allow T cell receptors to avidly and specifically bind epitopes containing non-peptidic side chains.
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U2 - 10.1074/jbc.272.13.8505
DO - 10.1074/jbc.272.13.8505
M3 - Article
C2 - 9079679
AN - SCOPUS:0344381263
SN - 0021-9258
VL - 272
SP - 8505
EP - 8514
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -