Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific...

Using both 'reverse genetics' and structural analysis, we have examined the in vivo relationship between antigenicity and T cell receptor (TCR) repertoire diversity. Influenza A virus infection of C57BL/6 mice induces profoundly different TCR repertoires specific for the nucleoprotein peptide of amino acids 366-374 (NP366) and the acid polymerase peptide of amino acids 224-233 (PA224) presented by H-2D(b). Here we show the H-2D(b)-NP366 complex with a 'featureless' structure selected a limited TCR repertoire characterized by 'public' TCR usage. In contrast, the prominent H-2D(b)-PA224 complex selected diverse, individually 'private' TCR repertoires. Substitution of the arginine at position 7 of PA224 with an alanine reduced the accessible side chains of the epitope. Infection with an engineered virus containing a mutation at the site encoding the exposed arginine at position 7 of PA224 selected a restricted TCR repertoire similar in diversity to that of the H-2D(b)-NP366-specific response. Thus, the lack of prominent features in an antigenic complex of peptide and major histocompatibility complex class I is associated with a diminished spectrum of TCR usage.