TCRs with Distinct Specificity Profiles Use Different Binding Modes to Engage an Identical Peptide-HLA Complex.
J Immunol
; 204(7): 1943-1953, 2020 04 01.
Article
in En
| MEDLINE
| ID: mdl-32102902
ABSTRACT
The molecular rules driving TCR cross-reactivity are poorly understood and, consequently, it is unclear the extent to which TCRs targeting the same Ag recognize the same off-target peptides. We determined TCR-peptide-HLA crystal structures and, using a single-chain peptide-HLA phage library, we generated peptide specificity profiles for three newly identified human TCRs specific for the cancer testis Ag NY-ESO-1157-165-HLA-A2. Two TCRs engaged the same central peptide feature, although were more permissive at peripheral peptide positions and, accordingly, possessed partially overlapping peptide specificity profiles. The third TCR engaged a flipped peptide conformation, leading to the recognition of off-target peptides sharing little similarity with the cognate peptide. These data show that TCRs specific for a cognate peptide recognize discrete peptide repertoires and reconciles how an individual's limited TCR repertoire following negative selection in the thymus is able to recognize a vastly larger antigenic pool.
Full text:
1
Database:
MEDLINE
Main subject:
Peptides
/
Receptors, Antigen, T-Cell
/
HLA-A2 Antigen
/
Histocompatibility Antigens
Limits:
Humans
Language:
En
Year:
2020
Type:
Article