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Several HLA alleles share overlapping peptide specificities

Item Type:Article
Title:Several HLA alleles share overlapping peptide specificities
Creators Name:Sidney, J. and del Guercio, M.F. and Southwood, S. and Engelhard, V.H. and Appella, E. and Rammensee, H.G. and Falk, K. and Roetzschke, O. and Takiguchi, M. and Kubo, R.T.
Abstract:Herein we describe the establishment of assays to measure peptide binding to purified HLA-B*0701, -B*0801, -B*2705, -B*3501-03, -B*5401, -Cw*0401, -Cw*0602, and -Cw*0702 molecules. The binding of known peptide epitopes or naturally processed peptides correlates well with HLA restriction or origin, underscoring the immunologic relevance of these assays. Analysis of the sequences of various HLA class I alleles suggested that alleles with peptide motifs characterized by proline in position 2 and aromatic or hydrophobic residues at their C-terminus shared key consensus residues at positions 9, 63, 66, 67, and 70 (B pocket) and residue 116 (F pocket). Prediction of the peptide-binding specificity of HLA-B*5401, on the basis of this consensus B and F pocket structure, verified this hypothesis and suggested that a relatively large family of HLA-B alleles (which we have defined as the HLA-B7-like supertype) may significantly overlap in peptide binding specificity. Availability of quantitative binding assays allowed verification that, indeed, many (25%) of the peptide ligands carrying proline in position 2 and hydrophobic/aromatic residues at the C-terminus (the B7-like supermotif) were capable of binding at least three of five HLA-B7-like supertype alleles. Identification of epitopes carrying the B7-like supermotif and binding to a family of alleles represented in over 40% of individuals from all major ethnic groups may be of considerable use in the design of peptide vaccines.
Keywords:Alleles, Amino Acid Sequence, Transformed Cell Line, Consensus Sequence, Epitopes, MHC Class I Genes, HLA-B Antigens, Molecular Sequence Data, Peptide Fragments, Protein Binding, Tertiary Protein Structure, Structure-Activity Relationship, Substrate Specificity
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:154
Number:1
Page Range:247-259
Date:1 January 1995
Official Publication:http://www.jimmunol.org/cgi/content/abstract/154/1/247
PubMed:View item in PubMed

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