αβ T cell receptors that do not undergo major histocompatibility complex-specific thymic selection possess antibody-like recognition specificities.
Major histocompatibility complex (MHC) restriction is the cardinal feature of T cell antigen recognition and is thought to be intrinsic to αβ T cell receptor (TCR) structure because of germline-encoded residues that impose MHC specificity. Here, we analyzed αβTCRs from T cells that had not undergone MHC-specific thymic selection. Instead of recognizing peptide-MHC complexes, the two αβTCRs studied here resembled antibodies in recognizing glycosylation-dependent conformational epitopes on a native self-protein, CD155, and they did so with high affinity independently of MHC molecules. Ligand recognition was via the αβTCR combining site and involved the identical germline-encoded residues that have been thought to uniquely impose MHC specificity, demonstrating that these residues do not only promote MHC binding. This study demonstrates that, without MHC-specific thymic selection, αβTCRs can resemble antibodies in recognizing conformational epitopes on MHC-independent ligands.
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Anastasia N
AN
Tikhonova
François
F
Van Laethem
Ken-ichi
K
Hanada
Jinghua
J
Lu
Leonid A
LA
Pobezinsky
Changwan
C
Hong
Terry I
TI
Guinter
Susanna K
SK
Jeurling
Günter
G
Bernhardt
Jung-Hyun
JH
Park
James C
JC
Yang
Peter D
PD
Sun
Alfred
A
Singer
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D017353:Gene Deletion; D008024:Ligands; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011991:Receptors, Virus; C066100:poliovirus receptor