Allogeneic T lymphocytes as a source of peptide-dependent T cells specific for myeloma cells.
We investigated the generation of myeloma-specific CTLs from normal donors HLA mismatched with the myeloma cell line SBN. The T-cell line obtained was cloned and each CTL was assessed against SBN and SBN-EBV (a B-EBV cell line obtained by EBV infection of B cells from SBN patient) simultaneously. Among >270 clones evaluated, 2 CTLs (Vbeta13.1 and Vbeta17) killed SBN but spared SBN-EBV cells. Antibodies against HLA-I, but not HLA-A2, molecules abrogated their recognition of SBN. Moreover, SBN recognition was abrogated by anti-HLA-Cw6 antiserum. Both clones recognized two other HLA-Cw*0602 myeloma cell lines. Neither of them recognized HLA-Cw*0602 B-EBV cell lines, the PBMCs of HLA-Cw*0602-unrelated donors or HLA-Cw*0602 melanoma cell lines. We showed that HLA-Cw6 molecules were more expressed at the cell surface of B-EBV cells as compared with myeloma cells, suggesting that the lack of reactivity against B-EBV cells was not related to a low level of HLA expression. Since CTL clones did not express any KIR or NKG2D, we excluded the fact that NK cell receptors could be involved in myeloma-specific recognition through KIR-HLA-I or NKG2D-MICA,B interactions. Cold target competition and acid elution experiments confirmed that myeloma cell recognition was peptide dependent.
Geffroy-Luseau
Alexandrine
A
Inserm UMR601, Institut de Biologie, 9 quai Moncousu, 44093 Nantes cedex 01, France.
Moreau-Aubry
Agnès
A
Bataille
Régis
R
Pellat-Deceunynck
Catherine
C
D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D009101:Multiple Myeloma / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D010455:Peptides