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Critical Contribution of β Chain Residue 57 in Peptide Binding Ability of Both HLA-DR and -DQ Molecules

Nepom, Barbara S. ; Nepom, Gerald T. ; Coleman, Marilyn ; Kwok, William W.

Proceedings of the National Academy of Sciences - PNAS, 1996-07, Vol.93 (14), p.7202-7206 [Periódico revisado por pares]

United States: National Academy of Sciences of the United States of America

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Título:
Critical Contribution of β Chain Residue 57 in Peptide Binding Ability of Both HLA-DR and -DQ Molecules
Autor: Nepom, Barbara S. ; Nepom, Gerald T. ; Coleman, Marilyn ; Kwok, William W.
Assuntos: Alleles ; Amino Acid Sequence ; Amino acids ; Aspartic Acid ; Autoimmune diseases ; B-Lymphocytes ; Binding Sites ; Biological Evolution ; Cell Line ; Cell lines ; Codons ; Conserved Sequence ; HLA-DQ Antigens - chemistry ; HLA-DQ Antigens - genetics ; HLA-DQ Antigens - immunology ; HLA-DQ beta-Chains ; HLA-DR Antigens - chemistry ; HLA-DR Antigens - genetics ; HLA-DR Antigens - immunology ; Humans ; Immunology ; Medical immunity ; Molecular chains ; Molecular interactions ; Molecular Sequence Data ; Molecules ; Oligopeptides - chemistry ; Oligopeptides - immunology ; Peptides ; Polymorphism, Genetic ; Salts
É parte de: Proceedings of the National Academy of Sciences - PNAS, 1996-07, Vol.93 (14), p.7202-7206
Notas: ObjectType-Article-2
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Descrição: Position 57 in the β chain of HLA class II molecules maintains an Asp/non-Asp dimorphism that has been conserved through evolution and is implicated in susceptibility to some autoimmune diseases. The latter effect may be due to the influence of this residue on the ability of class II alleles to bind specific pathogenic peptides. We utilized highly homologous pairs of both DR and DQ alleles that varied at residue 57 to investigate the impact of this dimorphism on binding of model peptides. Using a direct binding assay of biotinylated peptides on whole cells expressing the desired alleles, we report several peptides that bind differentially to the allele pairs depending on the presence or absence of Asp at position 57. Peptides with negatively charged residues at anchor position 9 bind well to alleles not containing Asp at position 57 in the β chain but cannot bind well to homologous Asp-positive alleles. By changing the peptides at the single residue predicted to interact with this position 57, we demonstrate a drastically altered or reversed pattern of binding. Ala analog peptides confirm these interactions and identify a limited set of interaction sites between the bound peptides and the class II molecules. Clarification of the impact of specific class II polymorphisms on generating unique allele-specific peptide binding ``repertoires'' will aid in our understanding of the development of specific immune responses and HLA-associated diseases.
Editor: United States: National Academy of Sciences of the United States of America
Idioma: Inglês

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Critical Contribution of β Chain Residue 57 in Peptide Binding Ability of Both HLA-DR and -DQ Molecules

Nepom, Barbara S. ; Nepom, Gerald T. ; Coleman, Marilyn ; Kwok, William W.

United States: National Academy of Sciences of the United States of America

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