Unknown

Dataset Information

0

Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability.


ABSTRACT: alphabeta T cell receptors (TCRs) are genetically restricted to corecognize peptide antigens bound to self-major histocompatibility complex (pMHC) molecules; however, the basis for this MHC specificity remains unclear. Despite the current dogma, evaluation of the TCR-pMHC-I structural database shows that the nongermline-encoded complementarity-determining region (CDR)-3 loops often contact the MHC-I, and the germline-encoded CDR1 and -2 loops frequently participate in peptide-mediated interactions. Nevertheless, different TCRs adopt a roughly conserved docking mode over the pMHC-I, in which three MHC-I residues (65, 69, and 155) are invariably contacted by the TCR in one way or another. Nonetheless, the impact of mutations at these three positions, either individually or together, was not uniformly detrimental to TCR recognition of pHLA-B*0801 or pHLA-B*3508. Moreover, when TCR-pMHC-I recognition was impaired, this could be partially restored by expression of the CD8 coreceptor. The structure of a TCR-pMHC-I complex in which these three (65, 69, and 155) MHC-I positions were all mutated resulted in shifting of the TCR footprint relative to the cognate complex and formation of compensatory interactions. Collectively, our findings reveal the inherent adaptability of the TCR in maintaining peptide recognition while accommodating changes to the central docking site on the pMHC-I.

SUBMITTER: Burrows SR 

PROVIDER: S-EPMC2890827 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability.

Burrows Scott R SR   Chen Zhenjun Z   Archbold Julia K JK   Tynan Fleur E FE   Beddoe Travis T   Kjer-Nielsen Lars L   Miles John J JJ   Khanna Rajiv R   Moss Denis J DJ   Liu Yu Chih YC   Gras Stephanie S   Kostenko Lyudmila L   Brennan Rebekah M RM   Clements Craig S CS   Brooks Andrew G AG   Purcell Anthony W AW   McCluskey James J   Rossjohn Jamie J  

Proceedings of the National Academy of Sciences of the United States of America 20100518 23


alphabeta T cell receptors (TCRs) are genetically restricted to corecognize peptide antigens bound to self-major histocompatibility complex (pMHC) molecules; however, the basis for this MHC specificity remains unclear. Despite the current dogma, evaluation of the TCR-pMHC-I structural database shows that the nongermline-encoded complementarity-determining region (CDR)-3 loops often contact the MHC-I, and the germline-encoded CDR1 and -2 loops frequently participate in peptide-mediated interactio  ...[more]

Similar Datasets

| S-EPMC3887192 | biostudies-literature
| S-EPMC3160269 | biostudies-literature
| PRJNA862637 | ENA
| S-EPMC5407768 | biostudies-literature
| S-EPMC2570882 | biostudies-literature
| S-EPMC4426292 | biostudies-literature
| S-EPMC3874790 | biostudies-literature
| S-EPMC2636556 | biostudies-literature
| S-EPMC8456106 | biostudies-literature
| S-EPMC2193773 | biostudies-literature