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

作者：Holland Christopher J; Rizkallah Pierre J; Vollers Sabrina; Calvo Calle J Mauricio; Madura Florian; Fuller Anna; Sewell Andrew K; Stern Lawrence J; Godkin Andrew; Cole David K^*

来源：Scientific Reports, 2012, 2(1): 629.

DOI：10.1038/srep00629

Successful immunity requires that a limited pool of alpha beta T-cell receptors (TCRs) provide cover for a vast number of potential foreign peptide antigens presented by %26apos;self%26apos; 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.

• 出版日期2012-9-4