Peptide selection by an MHC H-2Kb class I molecule devoid of the central anchor ('C') pocket

Alberto Molano, Hediye Erdjument-Bromage, Daved H. Fremont, Ilhem Messaoudi, Paul Tempst, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The peptide-binding site of the murine MHC class I molecule H-2Kb contains a deep C pocket, that is critical for peptide binding, as it accepts the anchor phenylalanine or tyrosine residue located in the middle (position 5, P5F/Y) of H-2Kb binding peptides. H-2Kb predominantly binds octameric peptides. By both criteria, H-2Kb is unique among the known murine and class I molecule, none of which have a deep C pocket or preferentially select octamers. We investigated the relative importance of the C pocket in peptide selection and binding by the MHC. An MHC class I H-2Kb variant, K(bW9), predicted to contain no C pocket, was engineered by replacing valine at MHC9 with tryptophan. This mutation drastically altered the selection of peptides bound to K(bW9). The K(bW9) molecule predominantly, if not exclusively, bound nonamers. New peptide anchor residues substituted for the loss of the P5F/Y:C pocket interaction. P3P/Y, which plays an auxiliary role in binding to Kb, assumed the role of a primary anchor, and P5R was selected as a new primary anchor, most likely contacting the E pocket. These experiments demonstrate that the presence of a deep C pocket is responsible for the selection of octameric peptides as the preferred ligands for Kb and provide insight into the adaptation of peptides to a rearranged MHC groove.

Original languageEnglish (US)
Pages (from-to)2815-2823
Number of pages9
JournalJournal of Immunology
Volume160
Issue number6
StatePublished - Mar 15 1998
Externally publishedYes

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Peptides
Valine
Phenylalanine
Tryptophan
Tyrosine
Binding Sites
Ligands
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Molano, A., Erdjument-Bromage, H., Fremont, D. H., Messaoudi, I., Tempst, P., & Nikolich-Zugich, J. (1998). Peptide selection by an MHC H-2Kb class I molecule devoid of the central anchor ('C') pocket. Journal of Immunology, 160(6), 2815-2823.

Peptide selection by an MHC H-2Kb class I molecule devoid of the central anchor ('C') pocket. / Molano, Alberto; Erdjument-Bromage, Hediye; Fremont, Daved H.; Messaoudi, Ilhem; Tempst, Paul; Nikolich-Zugich, Janko.

In: Journal of Immunology, Vol. 160, No. 6, 15.03.1998, p. 2815-2823.

Research output: Contribution to journalArticle

Molano, A, Erdjument-Bromage, H, Fremont, DH, Messaoudi, I, Tempst, P & Nikolich-Zugich, J 1998, 'Peptide selection by an MHC H-2Kb class I molecule devoid of the central anchor ('C') pocket', Journal of Immunology, vol. 160, no. 6, pp. 2815-2823.
Molano A, Erdjument-Bromage H, Fremont DH, Messaoudi I, Tempst P, Nikolich-Zugich J. Peptide selection by an MHC H-2Kb class I molecule devoid of the central anchor ('C') pocket. Journal of Immunology. 1998 Mar 15;160(6):2815-2823.
Molano, Alberto ; Erdjument-Bromage, Hediye ; Fremont, Daved H. ; Messaoudi, Ilhem ; Tempst, Paul ; Nikolich-Zugich, Janko. / Peptide selection by an MHC H-2Kb class I molecule devoid of the central anchor ('C') pocket. In: Journal of Immunology. 1998 ; Vol. 160, No. 6. pp. 2815-2823.
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