title: Essential differences in ligand presentation and T cell epitope recognition among HLA molecules of the HLA-B44 supertype.
abstract: Human leukocyte antigens (HLA) have long been grouped into supertypes to facilitate peptide-based immunotherapy. Analysis of several hundreds of peptides presented by all nine antigens of the HLA-B44 supertype (HLA-B*18, B*37, B*40, B*41, B*44, B*45, B*47, B*49 and B*50) revealed unique peptide motifs for each of them. Taking all supertype members into consideration only 25 out of 670 natural ligands were found on more than one HLA molecule. Further direct comparisons by two mass spectrometric methods--isotope labeling as well as a label-free approach--consistently demonstrated only minute overlaps of below 3% between the ligandomes of different HLA antigens. In addition, T cell reactions of healthy donors against immunodominant HLA-B*44 and HLA-B*40 epitopes from EBV lacked promiscuous T-cell recognition within the HLA-B44 supertype. Taken together, these results challenge the common paradigm of broadly presented epitopes within this supertype.
authors.affiliation: Department of Immunology, University of Tübingen, Tübingen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Hillen
authors.forename: Gabor
authors.initials: G
authors.lastname: Mester
authors.forename: Claudia
authors.initials: C
authors.lastname: Lemmel
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Weinzierl
authors.forename: Margret
authors.initials: M
authors.lastname: Müller
authors.forename: Dorothee
authors.initials: D
authors.lastname: Wernet
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
mesh_terms: D020816:Amino Acid Motifs; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015235:HLA-B Antigens / Q000737:chemistry / Q000276:immunology*; D059948:HLA-B44 Antigen; D006801:Humans; D008024:Ligands
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D008024:Ligands