Unknown

Dataset Information

0

T cell receptor cross-reactivity expanded by dramatic peptide-MHC adaptability.


ABSTRACT: T cell receptor cross-reactivity allows a fixed T cell repertoire to respond to a much larger universe of potential antigens. Recent work has emphasized the importance of peptide structural and chemical homology, as opposed to sequence similarity, in T cell receptor cross-reactivity. Surprisingly, though, T cell receptors can also cross-react between ligands with little physiochemical commonalities. Studying the clinically relevant receptor DMF5, we demonstrate that cross-recognition of such divergent antigens can occur through mechanisms that involve heretofore unanticipated rearrangements in the peptide and presenting MHC protein, including binding-induced peptide register shifts and extensions from MHC peptide binding grooves. Moreover, cross-reactivity can proceed even when such dramatic rearrangements do not translate into structural or chemical molecular mimicry. Beyond demonstrating new principles of T cell receptor cross-reactivity, our results have implications for efforts to predict and control T cell specificity and cross-reactivity and highlight challenges associated with predicting T cell reactivities.

SUBMITTER: Riley TP 

PROVIDER: S-EPMC6371774 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


T cell receptor cross-reactivity allows a fixed T cell repertoire to respond to a much larger universe of potential antigens. Recent work has emphasized the importance of peptide structural and chemical homology, as opposed to sequence similarity, in T cell receptor cross-reactivity. Surprisingly, though, T cell receptors can also cross-react between ligands with little physiochemical commonalities. Studying the clinically relevant receptor DMF5, we demonstrate that cross-recognition of such div  ...[more]

Similar Datasets

| S-EPMC6077720 | biostudies-literature
| S-EPMC3248800 | biostudies-literature
| S-EPMC5075794 | biostudies-literature
| S-EPMC2242494 | biostudies-literature
| S-EPMC4887163 | biostudies-literature
| S-EPMC2762195 | biostudies-literature
| S-EPMC2860844 | biostudies-literature
| S-EPMC4684756 | biostudies-literature
| S-EPMC9859041 | biostudies-literature
| S-EPMC1829260 | biostudies-literature