title: Microheterogeneity in HLA-B35 alleles influences peptide-dependent allorecognition by cytotoxic T cells but not binding of a peptide-restricted monoclonal antibody.
abstract: Strong peptide dependency of HLA-B*3501-specific alloreactive T-cell clones was observed in the recognition of cells bearing closely related B35 variants. The single amino acid exchange in the beta-pleated sheet of B*3503 completely abolished the responses of all clones, whereas an amino acid exchange in the alpha 2 helix of the newest B35 member (B*3508) only altered allorecognition of one T-cell clone, demonstrating the differential impact of these positions on peptide binding to B35 molecules. In contrast to T cells, a mAb (TU165) recognizing the B35 specificity in a peptide-dependent manner bound to the B35 variants irrespective of their sequence heterogeneity. However, quantitative binding differences were detected with cells bearing the same B35 alleles. This is most likely due to variations in the amount of peptide(s) that associates with B35 and forms the ligand seen by this mAb. These results reveal how naturally occurring single amino acid substitutions have led to generation of functionally distinct molecules of another multimember HLA class I cluster.
authors.affiliation: Institute for Immunology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Steinle
authors.forename: C
authors.initials: C
authors.lastname: Reinhardt
authors.forename: E
authors.initials: E
authors.lastname: Nössner
authors.forename: B
authors.initials: B
authors.lastname: Uchanska-Ziegler
authors.forename: A
authors.initials: A
authors.lastname: Ziegler
authors.forename: D J
authors.initials: DJ
authors.lastname: Schendel
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D005838:Genotype; D015797:HLA-B35 Antigen / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015797:HLA-B35 Antigen; D010455:Peptides