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Immunodominant and public T cell receptor (TCR) usage is relatively common in many viral diseases yet surprising in the context of the large naive TCR repertoire. We examined the highly conserved Vbeta17:Valpha10.2 JM22 T cell response to the influenza matrix peptide (58-66)-HLA-A*0201 (HLA-A2-flu) through extensive kinetic, thermodynamic, and structural analyses. We found several conformational adjustments that accompany JM22-HLA-A2-flu binding and identified a binding "hotspot" within the Vbeta domain of the TCR. Within this hotspot, key germline-encoded CDR1 and CDR2 loop residues and a crucial but commonly coded residue in the hypervariable region of CDR3 provide the basis for the substantial bias in the selection of the germline-encoded Vbeta17 domain. The chances of having a substantial number of T cells in the naive repertoire that have HLA-A2-flu-specific Vbeta17 receptors may consequently be relatively high, thus explaining the immunodominant usage of this clonotype.

Original publication

DOI

10.1016/j.immuni.2007.12.018

Type

Journal article

Journal

Immunity

Publication Date

02/2008

Volume

28

Pages

171 - 182

Keywords

Amino Acid Motifs, Animals, Crystallography, X-Ray, HLA-A Antigens, HLA-A2 Antigen, Humans, Immunodominant Epitopes, Influenza A virus, Models, Molecular, Mutant Proteins, Mutation, Protein Structure, Tertiary, Protein Subunits, Receptors, Antigen, T-Cell, alpha-beta, Structure-Activity Relationship, T-Lymphocytes, Viral Matrix Proteins