PMID- 8941875 OWN - NLM STAT- MEDLINE DCOM- 19970303 LR - 20221207 IS - 1067-5582 (Print) IS - 1067-5582 (Linking) VI - 19 IP - 5 DP - 1996 Sep TI - Differences in frequency distribution of HLA-A2 subtypes between North American and Italian white melanoma patients: relevance for epitope specific vaccination protocols. PG - 357-63 AB - Cytotoxic T lymphocytes (CTL) associated in vivo with tumor regression recognize the product of nonmutated genes expressed by most melanoma cells as peptides bound to human leukocyte antigen (HLA) molecules. Multiple HLA-A*0201 restricted peptides derived from melanoma associated antigens (MAA) have been described, and peptide-based vaccination protocols against melanoma are being developed worldwide for the treatment of HLA-A2 melanoma patients based on the assumption that most serologically typed HLA-A2+ individuals will be suitable for such vaccinations. Serologic typing of HLA-A2, however, encompasses a family of at least 17 related alleles recognized by molecular typing techniques and differing at one or more functional residues of the HLA class I molecule. We have recently shown that naturally occurring single-residue variants of HLA-A*0201 are responsible for significant differences in CTL response to MAA-peptide stimulation. Existing data for HLA-A*02 subtype frequencies among whites (who are most affected by melanoma) derive from analyses of Northern European and North American populations that are of similar heritage and predict an exceedingly rare (< 5%) frequency of non-HLA-A*0201 alleles. Melanoma however, affects other white populations in which the prevalence of HLA-A*02 alleles could be more variable. This study was done to identify HLA-A*02 subtypes and their prevalence in two ancestrally different white melanoma populations. HLA-A*02 subtype frequencies were compared by polymerase chain reaction between serologically HLA-A2+ melanoma patients referred for treatment to the Istituto Nazionale Tumori of Milan (n = 93), Italy or the National Cancer Institute, Bethesda, MD, U.S.A. (n = 100). This analysis demonstrated differences in subtype specificity and distribution between the two populations, with a significantly higher percentage of non HLA-A*0201 subtypes in the Italian population. Only 2% of serologically HLA-A2+ Northern American white melanoma patients did not express HLA-A*0201. In contrast, 15% of HLA-A2+ Italian patients were not HLA-A*0201 (p2 value = 0.001). As allele-specific/peptide-based vaccination protocols are presently pursued at several institutions, a proportion of patients might be inappropriately enrolled basing their eligibility on serologically defined HLA-typing. FAU - Player, M A AU - Player MA AD - National Cancer Institute, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Barracchini, K C AU - Barracchini KC FAU - Simonis, T B AU - Simonis TB FAU - Rivoltini, L AU - Rivoltini L FAU - Arienti, F AU - Arienti F FAU - Castelli, C AU - Castelli C FAU - Mazzocchi, A AU - Mazzocchi A FAU - Belli, F AU - Belli F FAU - Parmiani, G AU - Parmiani G FAU - Marincola, F M AU - Marincola FM LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Immunother Emphasis Tumor Immunol JT - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy JID - 9418950 RN - 0 (Cancer Vaccines) RN - 0 (Epitopes) RN - 0 (HLA-A2 Antigen) SB - IM MH - Amino Acid Sequence MH - Cancer Vaccines/*immunology MH - Epitopes/*immunology MH - Gene Frequency/*immunology MH - HLA-A2 Antigen/*immunology MH - Haplotypes/*immunology MH - Humans MH - Immunization Schedule MH - Italy/epidemiology MH - Melanoma/*immunology MH - North America/epidemiology MH - Skin Neoplasms/immunology MH - White People/*genetics EDAT- 1996/09/01 00:00 MHDA- 1996/09/01 00:01 CRDT- 1996/09/01 00:00 PHST- 1996/09/01 00:00 [pubmed] PHST- 1996/09/01 00:01 [medline] PHST- 1996/09/01 00:00 [entrez] AID - 10.1097/00002371-199609000-00005 [doi] PST - ppublish SO - J Immunother Emphasis Tumor Immunol. 1996 Sep;19(5):357-63. doi: 10.1097/00002371-199609000-00005.