Frequency of Human Leukocyte Antigen-A 24 Alleles in Patients With Melanoma Determined by Human Leukocyte Antigen-A Sequence-Based Typing

Maria P. Bettinotti, Regina D. Norris, Julia A. Hackett, Carolyn O. Thompson, Toni B. Simonis, David Stroncek, Francesco M. Marincola

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)282-287
Number of pages6
JournalJournal of Immunotherapy
Volume23
Issue number2
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • DNA sequencing
  • HLA-A class I typing
  • HLA-A24
  • Human clinical studies
  • Immunotherapy
  • Melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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