Two autologous melanoma-specific and MHC-restricted human T cell clones with identical intra-tumour reactivity do not share the same TCR Vα and Vβ gene families

M. Sensi, C. Castelli, A. Anichini, D. Grossberger, A. Mazzocchi, R. Mortarini, G. Parmiani

Research output: Contribution to journalArticlepeer-review

Abstract

Among tumour infiltrating lymphocytes (TIL) of a melanoma patient, A CD8+, WT31+ CTL clone (8B3) had been previously isolated which exhibited specific and MHC-restricted lytic activity against the autologous tumour. To molecularly characterize T cell receptor (TCR) α and β transcripts of clone 8B3, sequence analysis of several cDNA isolates was carried out. Such analysis indicated that the functional α and β chain of 8B3 are composed of Vα2.1/Jα/Cα and Vβ8.2/Dβ/Jβ1.2/Cβ1 gene segments. Eleven additional melanoma-reactive T cell clones from the same patient (one MHC-restricted and 10 MHC-unrestricted) were analysed for usage of the 8B3 Vα2 and Vβ8 gene segments by Northern blot hybridization. Neither the Vα2 nor the Vβ8 segments were used by 8D9, the second MHC-restricted melanoma-specific TIL clone that displayed intra-tumour reactivity identical to that of 8B3 recognizing only 4 out of 25 melanoma clones isolated from the same metastases. No Vβ8 expression was found among the MHC-unrestricted T cell clones and all but two (found in duplicate as 4C4 and 4A6) were also negative for Vα2 expression. Southern blot analysis revealed different TCR β chain rearrangements in most MHC-unrestricted T cell clones providing evidence of their independent derivation. Taken together these findings show that TCR of clone 8B3 is unique in composition and not shared by MHC-unrestricted melanoma-reactive T cell clones. The different set of Vα and Vβ families used by clone 8D9 further indicates that the TCR usage in the specific and MHC-restricted response to melanoma can be polyclonal.

Original languageEnglish
Pages (from-to)261-271
Number of pages11
JournalMelanoma Research
Volume1
Issue number4
Publication statusPublished - 1991

Keywords

  • Cytotoxic T cell clones
  • Melanoma
  • T cell receptor
  • Tumour-infiltrating lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Dermatology
  • Oncology

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