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Unexpected T-cell r...
Unexpected T-cell recognition of an altered peptide ligand is driven by reversed thermodynamics
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- Allerbring, E. B. (author)
- Karolinska Institutet
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- Duru, A. D. (author)
- Karolinska Institutet
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- Uchtenhagen, H. (author)
- Karolinska Institutet
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Madhurantakam, C. (author)
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Tomek, M. B. (author)
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- Grimm, Sebastian (author)
- KTH,Molekylär Bioteknologi
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Mazumdar, P. A. (author)
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- Friemann, Rosmarie, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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- Uhlin, M. (author)
- Karolinska Institutet
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- Sandalova, T. (author)
- Karolinska Institutet
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- Nygren, Per-Åke (author)
- KTH,Molekylär Bioteknologi
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Achour, A. (author)
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(creator_code:org_t)
- 2012-09-20
- 2012
- English.
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 42:11, s. 2990-3000
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Abstract
Subject headings
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- The molecular basis underlying T-cell recognition of MHC molecules presenting altered peptide ligands is still not wellestablished. A hierarchy of T-cell activation by MHC class I-restricted altered peptide ligands has been defined using the T-cell receptor P14 specific for H-2Db in complex with the immunodominant lymphocytic choriomeningitis virus peptide gp33 (KAVYNFATM). While substitution of tyrosine to phenylalanine (Y4F) or serine (Y4S) abolished recognition by P14, the TCR unexpectedly recognized H-2Db in complex with the alanine-substituted semiagonist Y4A, which displayed the most significant structural modification. The observed functional hierarchy gp33 > Y4A > Y4S = Y4F was neither due to higher stabilization capacity nor to differences in structural conformation. However, thermodynamic analysis demonstrated that while recognition of the full agonist H-2Db/gp33 was strictly enthalpy driven, recognition of the weak agonist H-2Db/Y4A was instead entropy driven with a large reduction in the favorable enthalpy term. The fourfold larger negative heat capacity derived for the interaction of P14 with H-2Db/gp33 compared with H-2Db/Y4A can possibly be explained by higher water entrapment at the TCR/MHC interface, which is also consistent with the measured opposite entropy contributions for the interactions of P14 with both MHCs. In conclusion, this study demonstrates that P14 makes use of different strategies to adapt to structural modifications in the MHC/peptide complex.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- MHC
- Molecular immunology
- Protein-protein interactions
- Structural biology
- TCR
- major histocompatibility complex
- receptor cross-reactivity
- structural
- basis
- tcr-binding
- crystal-structure
- high-affinity
- human
- beta(2)-microglobulin
- conformational-changes
- molecular-mechanisms
- viral escape
- MHC
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Allerbring, E. B ...
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Duru, A. D.
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Uchtenhagen, H.
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Madhurantakam, C ...
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Tomek, M. B.
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Grimm, Sebastian
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show more...
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Mazumdar, P. A.
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Friemann, Rosmar ...
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Uhlin, M.
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Sandalova, T.
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Nygren, Per-Åke
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Achour, A.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
- Articles in the publication
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European Journal ...
- By the university
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University of Gothenburg
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Royal Institute of Technology
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Karolinska Institutet