title: Allele-specific peptide presentation of human leukocyte antigens: implications for tumor immunotherapy.
abstract: BACKGROUND
  Human leukocyte antigen (HLA) class I plays a central role in the immune defense against microbes and tumors by presenting endogenously processed peptides to T-cells. Few studies have addressed the question as to what extent variants of the same allelic HLA group differ in their peptide motif.
  
  
  METHODS
  To answer this question for the HLA-A*66 family, which is a sub-group of the widespread serological HLA-A10 group, peptides eluted from recombinant A*6602 and A*6603 molecules were sequenced and have with data previously reported for A*6601.
  
  
  RESULTS
  The amino acid exchange between A*6602 and A*6603 (Gln70His) has no impact on the peptide motif. By contrast, the amino acid exchange Arg163Glu that distinguishes A*6601 from A*6602/6603 results in a change of the peptides preferentially bound.
  
  
  CONCLUSIONS
  Minor amino acid differences between HLA molecules may have a large impact on peptide presentation. For immunotherapy based on tumor-related peptides, it is crucial that the tumor specific peptide is presented by the patients' HLA molecules. For this reason, patients need to be typed not only at the HLA group level, but also at the allelic level.
authors.affiliation: Laboratory Dres. Fenner and Partners, D-20095 Hamburg, Germany. helsner@fennerlabor.de
authors.forename: Holger-Andreas
authors.initials: HA
authors.lastname: Elsner
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
authors.forename: Christina
authors.initials: C
authors.lastname: Bade-Döding
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics*; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000628:therapy*; D010802:Phylogeny; D020836:Protein Structure, Quaternary
chemical_list: D015234:HLA-A Antigens