The T-cell receptor is not hardwired to engage MHC ligands.
The bias of αβ T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that engagement with MHC ligands during thymocyte selection and peripheral T-cell activation imposes remarkably little constraint over TCR structure. Such versatility is more consistent with an opportunist, rather than a predetermined, mode of interface formation. This hypothesis was experimentally confirmed by expressing a hybrid TCR containing TCR-γ chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.
Molecular Immunology Section, Division of Immunology and Inflammation, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom. holland@ie-freiburg.mpg.de
Stephen J
SJ
Holland
Istvan
I
Bartok
Meriem
M
Attaf
Raphael
R
Genolet
Immanuel F
IF
Luescher
Eleni
E
Kotsiou
Ashkenaz
A
Richard
Edward
E
Wang
Matthew
M
White
David J
DJ
Coe
Jian-Guo
JG
Chai
Cristina
C
Ferreira
Julian
J
Dyson
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019070:Cell Lineage / Q000276:immunology; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D005854:Germ Cells / Q000276:immunology; D008024:Ligands; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D011995:Recombination, Genetic / Q000235:genetics; D012641:Selection, Genetic; D013950:Thymus Gland / Q000276:immunology
D022801:Complementarity Determining Regions; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta