Functional evidence that conserved TCR CDRα3 loop docking governs the cross-recognition of closely related peptide: Class I complexes

I. Messaoudi, J. LeMaoult, B. M. Metzner, M. J. Miley, D. H. Fremont, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The TCR recognizes its peptide:MHC (pMHC) ligand by assuming a diagonal orientation relative to the Mhc helices, but it is unclear whether and to what degree individual TCRs exhibit docking variations when contacting similar pMHC complexes. We analyzed monospecific and cross-reactive recognition by diverse TCRs of an immunodominant HVH-1 glycoprotein B epitope (HSV-8p) bound to two closely related Mhc class I molecules, H-2Kb and H-2Kbm8. Previous studies indicated that the pMHC portion likely to vary in conformation between the two complexes resided at the N-terminal part of the complex, adjacent to peptide residues 2-4 and the neighboring Mhc side chains. We found that Ctl clones sharing TCR β-chains exhibited disparate recognition patterns, whereas those with drastically different TCRβ-chains but sharing identical TCRα CDR3 loops displayed identical functional specificity. This suggested that the CDRα3 loop determines the Tcr specificity in our model, the conclusion supported by modeling of the Tcr over the actual HSV-8:Kb crystal structure. Importantly, these results indicate a remarkable conservation in CDRα3 positioning, and, therefore, in docking of diverse TCRαβ heterodimers onto variant peptide:class I complexes, implying a high degree of determinism in thymic selection and T cell activation.

Original languageEnglish (US)
Pages (from-to)836-843
Number of pages8
JournalJournal of Immunology
Volume167
Issue number2
StatePublished - Jul 15 2001
Externally publishedYes

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Peptides
Epitopes
Clone Cells
Ligands
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Functional evidence that conserved TCR CDRα3 loop docking governs the cross-recognition of closely related peptide : Class I complexes. / Messaoudi, I.; LeMaoult, J.; Metzner, B. M.; Miley, M. J.; Fremont, D. H.; Nikolich-Zugich, Janko.

In: Journal of Immunology, Vol. 167, No. 2, 15.07.2001, p. 836-843.

Research output: Contribution to journalArticle

Messaoudi, I. ; LeMaoult, J. ; Metzner, B. M. ; Miley, M. J. ; Fremont, D. H. ; Nikolich-Zugich, Janko. / Functional evidence that conserved TCR CDRα3 loop docking governs the cross-recognition of closely related peptide : Class I complexes. In: Journal of Immunology. 2001 ; Vol. 167, No. 2. pp. 836-843.
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