Epitopes described in "Identification of a novel HLA-B60-restricted T cell epitope of the minor histocompatibility antigen HA-1 locus."

Article Authors:Bregje Mommaas; Janine Kamp; Jan-Wouter Drijfhout; Nico Beekman; Ferry Ossendorp; Peter Van Veelen; Joke Den Haan; Els Goulmy; Tuna Mutis
Article Title:Identification of a novel HLA-B60-restricted T cell epitope of the minor histocompatibility antigen HA-1 locus.
Reference Detail
Reference ID:1020296
Abstract:The polymorphic minor histocompatibility Ag HA-1 locus encodes two peptides, HA-1(H) and HA-1(R), with a single amino acid difference. Whereas the immunogenicity of the HA-1(R) allele has not yet been shown, the nonameric HA-1(H) peptide induces HLA-A2-restricted cytotoxic T cells in vivo and in vitro. It is not known whether the mHag HA-1(H) or HA-1(R) associates with other HLA class I molecules. Therefore, the polymorphic regions of both HA-1 alleles were analyzed to identify HLA class I binding peptides that are properly processed by proteasomal degradation. Peptide binding analyses were performed for all nonameric HA-1(H/R) peptides for binding to nine HLA class I molecules with >10% prevalence in the Caucasian population and for seven nonameric/decameric HA-1(H/R) peptides predicted to bind to HLA-A3, -B14, and -B60. Only the nonameric KECVL(H)/(R)DDL and decameric KECVL(H)/(R)DDLL peptides showed strong and stable binding to HLA-B60. In vitro digestion of 29-aa-long HA-1 peptides by purified 20S proteasomes revealed proper cleavage at the COOH termini of both HLA-B60 binding HA-1(H) and HA-1(R) peptides. In subsequent analyses, dendritic cells pulsed with the nonameric HA-1(R) peptide did not induce CTLs that recognize the natural HLA-B60/HA-1(R) ligand. In contrast, dendritic cells pulsed with the nonameric HA-1(H) peptide induced IFN-gamma-secreting T cells specific for the natural HLA-B60/HA-1(H) ligand in three HLA-B60(+) HA-1(RR) individuals, demonstrating the immunogenicity of the HLA-B60/HA-1(H) ligand. In conclusion, this study shows a novel HLA-B60-restricted T cell epitope of the minor histocompatibility Ag HA-1 locus.
Reference Type:Literature
PubMed ID:12218130
Journal:J Immunol
Journal Volume:169
Article Pages:3131-6
Journal ISSN:0022-1767
Article Chemical List:Epitopes, T-Lymphocyte;HA-1 antigen;HLA-B Antigens;HLA-B60 antigen;Minor Histocompatibility Antigens;Multienzyme Complexes;Oligopeptides;Peptide Fragments;Histidine;Arginine;Cysteine Endopeptidases;Proteasome Endopeptidase Complex
Article MeSH List:Amino Acid Sequence; Arginine(metabolism); Cell Line; Cells, Cultured; Cysteine Endopeptidases(metabolism); Epitopes, T-Lymphocyte(isolation & purification; metabolism); HLA-B Antigens(genetics; metabolism); Histidine(metabolism); Humans; Hydrolysis; Lymphocyte Activation; Minor Histocompatibility Antigens(isolation & purification; metabolism); Minor Histocompatibility Loci; Molecular Sequence Data; Multienzyme Complexes(metabolism); Oligopeptides(chemical synthesis; isolation & purification; metabolism); Peptide Fragments(metabolism); Proteasome Endopeptidase Complex; Protein Binding(immunology); Transfection
Curation Last Updated:2014-10-03 22:10:38