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Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers.


ABSTRACT: Successful immunity requires that a limited pool of ?? T-cell receptors (TCRs) provide cover for a vast number of potential foreign peptide antigens presented by 'self' major histocompatibility complex (pMHC) molecules. Structures of unligated and ligated MHC class-I-restricted TCRs with different ligands, supplemented with biophysical analyses, have revealed a number of important mechanisms that govern TCR mediated antigen recognition. HA1.7 TCR binding to the influenza hemagglutinin antigen (HA(306-318)) presented by HLA-DR1 or HLA-DR4 represents an ideal system for interrogating pMHC-II antigen recognition. Accordingly, we solved the structure of the unligated HA1.7 TCR and compared it to both complex structures. Despite a relatively rigid binding mode, HA1.7 T-cells could tolerate mutations in key contact residues within the peptide epitope. Thermodynamic analysis revealed that limited plasticity and extreme favorable entropy underpinned the ability of the HA1.7 T-cell clone to cross-react with HA(306-318) presented by multiple MHC-II alleles.

SUBMITTER: Holland CJ 

PROVIDER: S-EPMC3432979 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers.

Holland Christopher J CJ   Rizkallah Pierre J PJ   Vollers Sabrina S   Calvo-Calle J Mauricio JM   Madura Florian F   Fuller Anna A   Sewell Andrew K AK   Stern Lawrence J LJ   Godkin Andrew A   Cole David K DK  

Scientific reports 20120904


Successful immunity requires that a limited pool of αβ T-cell receptors (TCRs) provide cover for a vast number of potential foreign peptide antigens presented by 'self' major histocompatibility complex (pMHC) molecules. Structures of unligated and ligated MHC class-I-restricted TCRs with different ligands, supplemented with biophysical analyses, have revealed a number of important mechanisms that govern TCR mediated antigen recognition. HA1.7 TCR binding to the influenza hemagglutinin antigen (H  ...[more]

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