Structural analysis of TCR-ligand interactions studied on H-2Kd-restricted cloned CTL specific for a photoreactive peptide derivative.
To study the interaction of the TCR with its ligand, the complex of a MHC molecule and an antigenic peptide, we modified a TCR contact residue of a H-2Kd-restricted antigenic peptide with photoreactive 4-azidobenzoic acid. The photoreactive group was a critical component of the epitope recognized by CTL clones derived from mice immunized with such a peptide derivative. The majority of these clones expressed V beta 1-encoded beta chains that were paired with J alpha TA28-encoded alpha chains. For one of these TCR, the photoaffinity labeled sites were mapped on the alpha chain as a J alpha TA28-encoded tryptophan and on the beta chain as a residue of the C' strand of V beta 1. Molecular modeling of this TCR suggested the presence of a hydrophobic pocket that harbors this tryptophan as well as a tyrosine on the C' strand of V beta 1 between which the photoreactive side chain inserts. It is concluded that this avid binding principle may account for the preferential selection of V beta 1 and J alpha TA28-encoded TCR.
Luescher
I F
IF
Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
Anjuère
F
F
Peitsch
M C
MC
Jongeneel
C V
CV
Cerottini
J C
JC
Romero
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001386:Azides; D001483:Base Sequence; D001665:Binding Sites; D002999:Clone Cells; D007114:Immunization; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D001386:Azides; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; C087164:4-azidobenzoic acid