PMID- 21872626 OWN - NLM STAT- MEDLINE DCOM- 20120206 LR - 20111017 IS - 1879-1166 (Electronic) IS - 0198-8859 (Linking) VI - 72 IP - 11 DP - 2011 Nov TI - Mismatches outside exons 2 and 3 do not alter the peptide motif of the allele group B*44:02P. PG - 1039-44 LID - 10.1016/j.humimm.2011.08.004 [doi] AB - Sequence variations outside exons 2 and 3 do not appear to affect the function of human leukocyte antigen (HLA) class I alleles. HLA-B*44:02:01:01 and -B*44:27 are considered functionally identical because they differ by a single amino acid substitution of Val > Ala at position 199, which is located in the alpha3 domain. To validate that HLA-B*44:02:01:01 and -B*44:27 represent functionally identical alleles that might reflect a permissive mismatch in hematopoetic stem cell transplantation (HSCT), we determined their peptide-binding features. B-lymphoblastic cells were lentivirally transduced with B*44:02 and B*44:27 constructs and soluble recombinant molecules were purified by affinity chromatography. Peptides were isolated and sequencing of single peptides was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LTQ-Orbitrap) technology. We demonstrate that the peptide motif of B*44:02(199Val) and B*44:27(199Ala) is identical. Both variants feature E at P2 and Y, F, or W at POmega in their ligands. Most of the identified peptides are 9 to 11 amino acids in length and approximately 20% of these ligands are shared between the alleles. Our results lead to the conclusion that B*44:02:01:01 and B*44:27 might have the same immune function, validating a theory that is now being used in deciding which donors to select in HSCT when there is no identical donor available. CI - Copyright (c) 2011 American Society for Histocompatibility and Immunogenetics. All rights reserved. FAU - Bade-Doeding, Christina AU - Bade-Doeding C AD - Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. bade-doeding.christina@mh-hannover.de FAU - Cano, Pedro AU - Cano P FAU - Huyton, Trevor AU - Huyton T FAU - Badrinath, Soumya AU - Badrinath S FAU - Eiz-Vesper, Britta AU - Eiz-Vesper B FAU - Hiller, Oliver AU - Hiller O FAU - Blasczyk, Rainer AU - Blasczyk R LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110810 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (HLA Antigens) RN - 0 (HLA-B Antigens) RN - 0 (HLA-B*44:27 antigen) RN - 0 (HLA-B44 Antigen) RN - 0 (Peptide Fragments) SB - IM MH - Amino Acid Motifs/genetics MH - B-Lymphocytes/cytology/immunology/*metabolism MH - Cell Line, Tumor MH - Chromatography, Affinity MH - Donor Selection MH - Exons/genetics MH - HLA Antigens/chemistry/genetics/*metabolism MH - HLA-B Antigens/genetics/metabolism MH - HLA-B44 Antigen/chemistry/genetics/*metabolism MH - *Hematopoietic Stem Cell Transplantation MH - Histocompatibility/immunology MH - Humans MH - Mutation/genetics MH - Peptide Fragments/genetics/immunology/*metabolism MH - Polymorphism, Genetic MH - Protein Binding/genetics/immunology MH - Tandem Mass Spectrometry MH - Transgenes/genetics EDAT- 2011/08/30 06:00 MHDA- 2012/02/07 06:00 CRDT- 2011/08/30 06:00 PHST- 2011/01/20 00:00 [received] PHST- 2011/07/31 00:00 [revised] PHST- 2011/08/04 00:00 [accepted] PHST- 2011/08/30 06:00 [entrez] PHST- 2011/08/30 06:00 [pubmed] PHST- 2012/02/07 06:00 [medline] AID - S0198-8859(11)00493-9 [pii] AID - 10.1016/j.humimm.2011.08.004 [doi] PST - ppublish SO - Hum Immunol. 2011 Nov;72(11):1039-44. doi: 10.1016/j.humimm.2011.08.004. Epub 2011 Aug 10.