Differential roles of T cell receptor alpha and beta chains in ligand binding among H-2Kd-restricted cytolytic T lymphocyte clones specific for a photoreactive Plasmodium berghei circumsporozoite peptide derivative.
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-2Kd-restricted cytolytic T lymphocyte clones from mice immunized with a Plasmodium berghei circumsporozoite peptide (PbCS) 252-260 (SYIPSAEKI) derivative containing photoreactive Nepsilon-[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 beta chains along with specific complementary determining region (CDR) 3beta regions but diverse alpha chain sequences. Surprisingly, all T cell receptors were preferentially photoaffinity labeled on the alpha chain. For a representative T cell receptor, the photoaffinity labeled site was located in the Valpha C-strand. Computer modeling suggested the presence of a hydrophobic pocket, which is formed by parts of the Valpha/Jalpha C-, F-, and G-strands and adjacent CDR3alpha 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.
Anjuère
F
F
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland.
Kuznetsov
D
D
Romero
P
P
Cerottini
J C
JC
Jongeneel
C V
CV
Luescher
I F
IF
D000345:Affinity Labels; D000595:Amino Acid Sequence; D000818:Animals; D016782:Apicomplexa; D002999:Clone Cells / Q000276:immunology; D003198:Computer Simulation; D006183:H-2 Antigens / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D010449:Peptide Mapping; D010777:Photochemistry; D010962:Plasmodium berghei; D015800:Protozoan Proteins / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D000345:Affinity Labels; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010446:Peptide Fragments; D015800:Protozoan Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C105341:Ser-Tyr-Ile-Pro-Ser-Ala-Glu-Lys-Ile protein, Plasmodium; C041595:circumsporozoite protein, Protozoan