The mode of ligand recognition by two peptide: MHC class I-specific monoclonal antibodies

Ilhem Messaoudi, Joël LeMaoult, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The Ig superfamily members TCR and B cell receptor (BCR) share high structural and amino acid homology, yet interact with Ags in a distinct manner. The overall shape of the TCR ligand is rather constant, with the variation coming from the MHC polymorphism and the peptide heterogeneity. Consequently, the TCR α- and β-chains form a relatively flat ligand-binding site that interacts with the peptide:MHC (pep:MHC) ligand in a fixed diagonal orientation relative to the MHC α-helices, with the α- and β-chains of the TCR contacting the N and C termini of the pep:MHC complex, respectively. By contrast, the shape of BCR ligands varies dramatically, and the BCR exhibits much greater variability of the Ag-binding site. The mAbs 25-D1.16 (D1) and 22-C5.9 (C5), specific for the OVA-8:H-2Kb complex, allowed us to directly compare how TCR and BCR approach the same ligand. To that effect, we mapped D1 and C5 footprints over the OVA-8:H-2Kb complex. Using peptide variants and mutant MHC molecules, we show that the D1 and C5 contacts with the OVA- 8:Kb complex C terminus overlap with the TCR β-chain footprint, but that this footprint also extends to the regions of the molecule not contacted by the TCR. These studies suggest that D1 and C5 exhibit a hybrid mode of pep:MHC recognition, in part similar to that of the TCR β-chain and in part similar to the conventional anti-MHC Ab.

Original languageEnglish (US)
Pages (from-to)3286-3294
Number of pages9
JournalJournal of Immunology
Volume163
Issue number6
StatePublished - Sep 15 1999
Externally publishedYes

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Monoclonal Antibodies
Ligands
B-Lymphocytes
Peptides
Binding Sites
Amino Acids
OVA-8

ASJC Scopus subject areas

  • Immunology

Cite this

The mode of ligand recognition by two peptide : MHC class I-specific monoclonal antibodies. / Messaoudi, Ilhem; LeMaoult, Joël; Nikolich-Zugich, Janko.

In: Journal of Immunology, Vol. 163, No. 6, 15.09.1999, p. 3286-3294.

Research output: Contribution to journalArticle

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