Functional heterogeneity of HLA-A*02 subtypes revealed by presentation of a MAGE-3-encoded peptide to cytotoxic T cell clones

Katharina Fleischhauer, Silvia Tanzarella, Vincenzo Russo, Maria Luisa Sensi, Pierre Van Der Bruggen, Claudio Bordignon, Catia Traversari

Research output: Contribution to journalArticle

Abstract

The peptide-binding and presentation characteristics of seven naturally occurring HLA-A2 subtypes were studied using M3 271, a peptide derived from the tumor-specific Ag encoded by gene MAGE-3, which has been shown to be processed and presented by A*0201 † melanoma lines. Three independent M3 271 -specific CTL clones were obtained from two unrelated A*0201† donors. B lymphoblastoid cell lines (BLCLs) expressing A*0201, A*0207, or A*0209 could be sensitized to lysis by all three clones upon incubation with the relevant peptide. Furthermore, the same BLCLs were able to present endogenous M3 271 in IFN-γ release assays. These findings demonstrate, for the first time, the existence of a functional overlap between A*0207 and other A*02 subtypes. One of the CTL clones also lysed M3 271 -pulsed BLCLs expressing A*0204 and A*0206, while the other two clones recognized M3 271 only in the context of either of these two subtypes. Peptide-pulsed BLCLs expressing A*0202 or A*0205 were not lysed, although A*0205 and, with lower affinity, A*0202 molecules were shown to bind peptide M3 271. These findings have implications for the selection of cancer patients for specific immunotherapy with peptide M3 271.

Original languageEnglish
Pages (from-to)2513-2521
Number of pages9
JournalJournal of Immunology
Volume159
Issue number5
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Immunology

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    Fleischhauer, K., Tanzarella, S., Russo, V., Sensi, M. L., Van Der Bruggen, P., Bordignon, C., & Traversari, C. (1997). Functional heterogeneity of HLA-A*02 subtypes revealed by presentation of a MAGE-3-encoded peptide to cytotoxic T cell clones. Journal of Immunology, 159(5), 2513-2521.