Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations.

Abstract:

: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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Turner SJ,Kedzierska K,Komodromou H,La Gruta NL,Dunstone MA,Webb AI,Webby R,Walden H,Xie W,McCluskey J,Purcell AW,Rossjohn J,Doherty PC

doi

10.1038/ni1175

keywords:

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

382-9

issue

4

eissn

1529-2908

issn

1529-2916

pii

ni1175

journal_volume

6

pub_type

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