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| Content Provider | Springer Nature Link |
|---|---|
| Author | Bade Doeding, Christina DeLuca, David S. Seltsam, Axel Blasczyk, Rainer Eiz Vesper, Britta |
| Copyright Year | 2007 |
| Abstract | There have been several attempts over the years to identify positions in the peptide-binding region (PBR) of human leukocyte antigens (HLA) that influence the specificity of bound amino acids (AAs) at each position in the peptide. Originally, six pockets (A–F) were defined by calculating the surface area of the PBR on the crystal structure of HLA-A2 molecules. More recent crystallographic analyses of a variety of HLA alleles have led to broader pocket definitions. In this study, we examined the peptide-binding specificity of HLA-B*41 alleles and compared our results with the available pocket definitions. By generating recombinant HLA-B molecules and studying the eluted peptides by mass spectrometry and pool sequencing, we detected two different PΩ peptide motifs within the B*41 group: Leu vs Val/Pro. Specificity was dependent on the presence of Leu (B*4102, B*4103, and B*4104) vs Trp (B*4101, B*4105, and B*4106) at AA position 95 in the HLA molecule, whose impact on PΩ has been a subject of controversy in current pocket definitions. In contrast, the Arg97Ser mutation did not affect pocket F binding specificity in B*41 subtypes although residue 97 was previously identified as a modulator of peptide binding for several HLA class I alleles. According to most pocket definitions, this study shows that the Asn80Lys substitution in B*4105 impels the peptide’s PΩ anchor toward more promiscuity. Our sequencing results of peptides eluted from HLA-B*41 variants demonstrate the limitations of current pocket definitions and underline the need for an extended peptide motif database for improved understanding of peptide–major histocompatibility complex interactions. |
| Starting Page | 253 |
| Ending Page | 259 |
| Page Count | 7 |
| File Format | |
| ISSN | 00937711 |
| Journal | Immunogenetics |
| Volume Number | 59 |
| Issue Number | 4 |
| e-ISSN | 14321211 |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2007-02-10 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Peptide-binding motif PΩ position Pocket definition Cell Biology Allergology Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Immunology |
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