TCR β-Chain Variable Region-Driven Selection and Massive Expansion of HLA-Class I-Restricted Antitumor CTL Lines from HLA-A*0201+ Melanoma Patients

Cristina Maccalli, Cinthia Farina, Marialuisa Sensi, Giorgio Parmiani, Andrea Anichini

Research output: Contribution to journalArticle

Abstract

Recognition of a given melanoma Ag involves a limited array of T cell clones bearing a structurally defined TCR. The aim of this study was to verify whether this information can be used to isolate and expand such anti-tumor effectors from fresh lymphocyte populations. We found that one to three different TCR β-chain variable (TCRBV) regions were significantly expanded in 4-wk mixed lymphocyte-tumor cultures (MLTC) from six HLA-A*0201+ melanoma patients, and that the T cells expressing the expanded TCRBV regions were involved in HLA class I-restricted lysis of the tumor. T cell activation by mAbs to MLTC-selected TCRBV region and CD28 resulted in large scale expansion (1-10 × 109 cells) of T cell lines, highly enriched for the expression of a single TCRBV region and for CD8+ T cells. The TCRBV-driven selection was equally effective when applied to patients' or healthy donors' lymphocytes, and the T cell lines isolated from melanoma patients exerted HLA class I-restricted lysis of the autologous tumor. MLTC and TCRBV-selected lines recognized allogeneic melanomas sharing HLA-A and -B alleles with the autologous tumor, but only two of the HLA-A2-restricted lines were directed to a known peptide from melanoma-associated Ags. Single-strand conformation polymorphism analysis indicated a polyclonal composition of both MLTC and TCRBV-selected lines, but expansion of clonotypes with identical CDR3 length was observed only in the MLTC lines. Thus, TCRBV-driven selection can be exploited to obtain large scale expansion of antitumor CTL lines from melanoma patients.

Original languageEnglish
Pages (from-to)5902-5913
Number of pages12
JournalJournal of Immunology
Volume158
Issue number12
Publication statusPublished - Jun 15 1997

ASJC Scopus subject areas

  • Immunology

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