PDBsum entry 2ypl

Immune system/viral protein

PDB id: 2ypl

Contents

Protein chains

274 a.a.

99 a.a.

11 a.a.

199 a.a.

238 a.a.

Waters ×195

References listed in PDB file

Key reference

• Title: Structural features underlying t-Cell receptor sensitivity to concealed mhc class i micropolymorphisms.
• Authors: G.B.Stewart-Jones, P.Simpson, P.A.Van der merwe, P.Easterbrook, A.J.Mcmichael, S.L.Rowland-Jones, E.Y.Jones, G.M.Gillespie.
• Ref.: Proc Natl Acad Sci U S A, 2012, 109, E3483.
• PubMed id: 23161907

Abstract

Polymorphic differences distinguishing MHC class I subtypes often permit the presentation of shared epitopes in conformationally identical formats but can affect T-cell repertoire selection, differentially impacting autoimmune susceptibilities and viral clearance in vivo. The molecular mechanisms underlying this effect are not well understood. We performed structural, thermodynamic, and functional analyses of a conserved T-cell receptor (TCR) which is frequently expanded in response to a HIV-1 epitope when presented by HLA-B*5701 but is not selected by HLA-B*5703, which differs from HLA-B*5701 by two concealed polymorphisms. Our findings illustrate that although both HLA-B*57 subtypes display the epitope in structurally conserved formats, the impact of their polymorphic differences occurs directly as a consequence of TCR ligation, primarily because of peptide adjustments required for TCR binding, which involves the interplay of polymorphic residues and water molecules. These minor differences culminate in subtype-specific differential TCR-binding kinetics and cellular function. Our data demonstrate a potential mechanism whereby the most subtle MHC class I micropolymorphisms can influence TCR use and highlight their implications for disease outcomes.