Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules

Jörg Ruppert, John Sidney, Esteban Celis, Ralph T. Kubo, Howard M. Grey, Alessandro Sette

Research output: Contribution to journalArticle

568 Citations (Scopus)

Abstract

The functional determinants of histocompatibility leukocyte antigen (HLA)-A2.1-peptide interactions have been detailed by the use of quantitative molecular binding assays and a chemically synthesized library of naturally occurring epitopes. The importance of hydrophobic anchor residues in position 2 and the C-terminus was confirmed. These anchors are necessary, but not sufficient, for high affinity binding, as the predictions based solely on these anchors are only about 30% accurate. Prominent roles for several other positions (1, 3, and 7) were also demonstrated. The location of these residues within the peptides matches secondary A2.1 pockets previously demonstrated by X-ray crystallography. From a functional standpoint, similar dominant negative effects on binding were observed for charged residues in both nonamers and decamers, while positive effects differed between nonamers and decamers. An extended motif taking into account secondary anchors increased the predictability of A2.1-binding epitopes to a level of 70%, underscoring the practical usefulness of extended motifs.

Original languageEnglish (US)
Pages (from-to)929-937
Number of pages9
JournalCell
Volume74
Issue number5
DOIs
StatePublished - Sep 10 1993
Externally publishedYes

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Histocompatibility Antigens
HLA Antigens
Anchors
Epitopes
Peptides
Molecules
X Ray Crystallography
X ray crystallography
Assays

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. / Ruppert, Jörg; Sidney, John; Celis, Esteban; Kubo, Ralph T.; Grey, Howard M.; Sette, Alessandro.

In: Cell, Vol. 74, No. 5, 10.09.1993, p. 929-937.

Research output: Contribution to journalArticle

Ruppert, Jörg ; Sidney, John ; Celis, Esteban ; Kubo, Ralph T. ; Grey, Howard M. ; Sette, Alessandro. / Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. In: Cell. 1993 ; Vol. 74, No. 5. pp. 929-937.
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