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. 1991 Dec 15;88(24):11325–11329. doi: 10.1073/pnas.88.24.11325

Positioning of a peptide in the cleft of HLA-A2 by complementing amino acid changes.

F Latron 1, R Moots 1, J B Rothbard 1, T P Garrett 1, J L Strominger 1, A McMichael 1
PMCID: PMC53127  PMID: 1763045

Abstract

Several mutant HLA-A2 molecules have been constructed and expressed in the mutant human B-cell line C1R, which lacks HLA-A and HLA-B antigens, and examined for presentation of a previously defined peptide epitope derived from the influenza matrix protein to appropriate human cytotoxic T-lymphocyte lines. When leucine residue 66 in this matrix peptide containing residues 57-68 (matrix peptide 57-68) was replaced by arginine, the resulting matrix peptide 57-68 R66 was not presented to HLA-A2, but the mutation Y116D (tyrosine to aspartic acid at residue 116) in the floor of the peptide binding cleft near its right end dramatically restored peptide presentation. A similar result was obtained by substitution of ornithine for leucine at residue 66. These data provide strong support for a model in which the peptide is orientated with its amino terminus at the left end of the cleft of HLA-A2 and its carboxyl terminus at the right.

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Selected References

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