Back to Search
Start Over
A single amino-acid polymorphism in pocket A of HLA-A*6602 alters the auxiliary anchors compared with HLA-A*6601 ligands.
- Source :
-
Immunogenetics [Immunogenetics] 2004 May; Vol. 56 (2), pp. 83-8. Date of Electronic Publication: 2004 Apr 30. - Publication Year :
- 2004
-
Abstract
- In this study we have sequenced peptides eluted from a truncated recombinant HLA-A*6602 molecule, and compared their features with data reported for peptides presented in the A*6601 molecule. A striking change in the amino-acid binding preferences was observed at peptide position P1, which interacts with pocket A of the HLA peptide-binding region. For A*6601, aspartic acid and glutamic acid, both of which possess polar acidic side-chains, have been described as auxiliary anchors. This is in marked contrast to A*6602, where we observed serine, which has a neutral polar side-chain, as auxiliary anchor at P1. Accordingly, this shift in the physico-chemical properties of the auxiliary anchor may be best explained by the HLA amino-acid polymorphism at position 163, where arginine (hydrophilic, alkaline) in A*6601 has been replaced by glutamic acid in A*6602. This amino-acid exchange results in a shift towards higher acidity in pocket A, apparently resulting in the loss of preference for acidic auxiliary anchors, and leading to the preference for the neutral amino acid serine. The change of the auxiliary anchor residue at P1 is likely to alter the spectrum of peptides presented by A*6602 compared with A*6601, which may result in allogenicity in the case of a mismatch in allogeneic stem cell transplantation.
- Subjects :
- Arginine genetics
Arginine metabolism
Aspartic Acid genetics
Aspartic Acid metabolism
Chromatography, Affinity
Glutamic Acid genetics
Glutamic Acid metabolism
HLA-A Antigens metabolism
Humans
Peptide Fragments chemistry
Peptide Fragments genetics
Peptide Fragments metabolism
Protein Binding genetics
Recombinant Proteins genetics
Recombinant Proteins metabolism
Serine genetics
Serine metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
HLA-A Antigens genetics
Ligands
Polymorphism, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0093-7711
- Volume :
- 56
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Immunogenetics
- Publication Type :
- Academic Journal
- Accession number :
- 15118850
- Full Text :
- https://doi.org/10.1007/s00251-004-0677-y