T cell receptor cross-reactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility

Journal Article · Tue Sep 07 04:00:00 EDT 2010 · Immunity

DOI:https://doi.org/10.1016/j.immuni.2009.11.003· OSTI ID:1006173

Borbulevych, O Y; Piepenbrink, K H; Gloor, B E; Scott, D R; Sommese, R F; Cole, D K; Sewell, A K; Baker, B M

T cell-mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The {alpha}{beta} TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were attributable to peptide and MHC molecular motion present in Tel1p-HLA-A2 but absent in Tax-HLA-A2. Differential tuning of the dynamic properties of HLA-A2 by the Tax and Tel1p peptides thus facilitates cross-recognition and impacts how structural diversity can be presented to and accommodated by receptors of the immune system.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1006173
• Journal Information: Immunity, Journal Name: Immunity Journal Issue: (6) ; 12, 2009 Vol. 31
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
BIOLOGICAL FUNCTIONS
IMMUNITY
MORPHOLOGY
PEPTIDES
RECEPTORS