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The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain.

Ishizuka J, Stewart-Jones GB, van der Merwe A, Bell JI, McMichael AJ, Jones EY
Immunity 28 171-82 (2008)
Related entries: 2vlj, 2vll, 2vlm, 2vlr

Cited: 87 times
EuropePMC logo PMID: 18275829

Abstract

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.

Reviews - 2vlk mentioned but not cited (1)

  1. Thermodynamics of T-cell receptor-peptide/MHC interactions: progress and opportunities. Armstrong KM, Insaidoo FK, Baker BM. J Mol Recognit 21 275-287 (2008)

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Reviews citing this publication (14)

  1. T cell antigen receptor recognition of antigen-presenting molecules. Rossjohn J, Gras S, Miles JJ, Turner SJ, Godfrey DI, McCluskey J. Annu Rev Immunol 33 169-200 (2015)
  2. T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity. Stone JD, Chervin AS, Kranz DM. Immunology 126 165-176 (2009)
  3. Bias in the αβ T-cell repertoire: implications for disease pathogenesis and vaccination. Miles JJ, Douek DC, Price DA. Immunol Cell Biol 89 375-387 (2011)
  4. Structural and biophysical determinants of αβ T-cell antigen recognition. Bridgeman JS, Sewell AK, Miles JJ, Price DA, Cole DK. Immunology 135 9-18 (2012)
  5. Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes. Armstrong KM, Piepenbrink KH, Baker BM. Biochem J 415 183-196 (2008)
  6. Cross-reactivity of T cells and its role in the immune system. Petrova G, Ferrante A, Gorski J. Crit Rev Immunol 32 349-372 (2012)
  7. A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons learned and much to be learned. Gras S, Burrows SR, Turner SJ, Sewell AK, McCluskey J, Rossjohn J. Immunol Rev 250 61-81 (2012)
  8. Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'. Rich RL, Myszka DG. J Mol Recognit 23 1-64 (2010)
  9. Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes. Singh NK, Riley TP, Baker SCB, Borrman T, Weng Z, Baker BM. J Immunol 199 2203-2213 (2017)
  10. Understanding the structural dynamics of TCR-pMHC complex interactions. Kass I, Buckle AM, Borg NA. Trends Immunol 35 604-612 (2014)
  11. Evolution and function of the TCR Vgamma9 chain repertoire: It's good to be public. Pauza CD, Cairo C. Cell Immunol 296 22-30 (2015)
  12. Lessons learned from natural infection: focusing on the design of protective T cell vaccines for HIV/AIDS. Ahlers JD, Belyakov IM. Trends Immunol 31 120-130 (2010)
  13. Using the T Cell Receptor as a Biomarker in Type 1 Diabetes. Nakayama M, Michels AW. Front Immunol 12 777788 (2021)
  14. An old Twist in HLA-A: CDR3α Hook up at an R65-joint. Murray JS. Front Immunol 6 268 (2015)

Articles citing this publication (67)



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