title: Mismatches outside exons 2 and 3 do not alter the peptide motif of the allele group B*44:02P.
abstract: 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 α3 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 PΩ 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.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. bade-doeding.christina@mh-hannover.de
authors.forename: Christina
authors.initials: C
authors.lastname: Bade-Doeding
authors.forename: Pedro
authors.initials: P
authors.lastname: Cano
authors.forename: Trevor
authors.initials: T
authors.lastname: Huyton
authors.forename: Soumya
authors.initials: S
authors.lastname: Badrinath
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
authors.forename: Oliver
authors.initials: O
authors.lastname: Hiller
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D046148:Donor Selection; D005091:Exons / Q000235:genetics; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism; D059948:HLA-B44 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility / Q000276:immunology; D006801:Humans; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D053719:Tandem Mass Spectrometry; D019076:Transgenes / Q000235:genetics
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; C471439:HLA-B*44:27 antigen; D059948:HLA-B44 Antigen; D010446:Peptide Fragments