Frequency of human leukocyte antigen-A 24 alleles in patients with melanoma determined by human leukocyte antigen-A sequence-based typing

The analysis of immune responses of patients with melanoma has led to the i dentification of melanoma-associated antigens targeted by T cells. Cytotoxi c T lymphocytes recognize peptides from melanoma-associated antigens presen ted on the cancer cell surface in the context of HLA class I molecules. Imm unodominant melanoma-associated antigen epitopes are being evaluated for th eir ability to immunize patients with advanced melanoma. However, these vac cination efforts are limited by the extensive polymorphism of the HLA class I heavy chain, which occurs in functional domains of the molecule. Patient s 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 fam ily 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 de termine the HLA-A alleles in genomic DNA. HLA-A 24 was also typed in health y persons of various ethnic backgrounds to further explore the HLA-A24 fami ly. In white persons, the HLA-A*2402 allele was most common (in 85% of whit e 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). Finall y, two new alleles, HLA-A*2422 and HLA-A*24 null, were identified. These re sults suggest that vaccination with HLA-A*2402-associated epitopes has the potential for broad use in this patient population.