title: Frequency of human leukocyte antigen-A 24 alleles in patients with melanoma determined by human leukocyte antigen-A sequence-based typing.
abstract: The analysis of immune responses of patients with melanoma has led to the identification of melanoma-associated antigens targeted by T cells. Cytotoxic T lymphocytes recognize peptides from melanoma-associated antigens presented on the cancer cell surface in the context of HLA class I molecules. Immunodominant melanoma-associated antigen epitopes are being evaluated for their ability to immunize patients with advanced melanoma. However, these vaccination efforts are limited by the extensive polymorphism of the HLA class I heavy chain, which occurs in functional domains of the molecule. Patients with melanoma with the HLA-A-24 phenotype were recruited for vaccination with the peptide AFLPWHRLF from the melanoma-associated antigen tyrosinase. This peptide is recognized in association with HLA-A*2402. The HLA-A24 family includes at least 15 alleles whose frequency and ability to present the same peptide are unknown. The distribution of HLA-A24 alleles was studied in a melanoma population for the practical purpose of identifying patients suitable for vaccination with HLA-A*2402 epitopes. An HLA-A locus-specific polymerase chain reaction method followed by sequencing was developed to determine the HLA-A alleles in genomic DNA. HLA-A 24 was also typed in healthy persons of various ethnic backgrounds to further explore the HLA-A24 family. In white persons, the HLA-A*2402 allele was most common (in 85% of white persons and in 97% of the patients with melanoma). Fewer persons carried the HLA-A*2403 allele (13% in all samples, 3% in melanoma patients). Finally, two new alleles, HLA-A*2422 and HLA-A*24 null, were identified. These results suggest that vaccination with HLA-A*2402-associated epitopes has the potential for broad use in this patient population.
authors.affiliation: Department of Transfusion Medicine, Clinical Center, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Bettinotti
authors.forename: R D
authors.initials: RD
authors.lastname: Norris
authors.forename: J A
authors.initials: JA
authors.lastname: Hackett
authors.forename: C O
authors.initials: CO
authors.lastname: Thompson
authors.forename: T B
authors.initials: TB
authors.lastname: Simonis
authors.forename: D
authors.initials: D
authors.lastname: Stroncek
authors.forename: F M
authors.initials: FM
authors.lastname: Marincola
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D015234:HLA-A Antigens / Q000097:blood / Q000235:genetics*; D059871:HLA-A24 Antigen; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D020539:Sequence Analysis, Protein; D014407:Tumor Cells, Cultured
chemical_list: D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D014442:Monophenol Monooxygenase