Article: article from journal or magazin.
Flow-microfluorometric monitoring of oligoclonal CD8+ T cell responses to an immunodominant Moloney leukemia virus-encoded epitope in vivo.
Journal of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
The TCR repertoire of CD8+ T cells specific for Moloney murine leukemia virus (M-MuLV)-associated Ags has been investigated in vitro and in vivo. Analysis of a large panel of established CD8+ CTL clones specific for M-MuLV indicated an overwhelming bias for V beta4 in BALB/c mice and for V beta5.2 in C57BL/6 mice. These V beta biases were already detectable in mixed lymphocyte:tumor cell cultures established from virus-immune spleen cells. Furthermore, direct ex vivo analysis of PBL from BALB/c or C57BL/6 mice immunized with syngeneic M-MuLV-infected tumor cells revealed a dramatic increase in CD8+ cells expressing V beta4 or V beta5.2, respectively. M-MuLV-specific CD8+ cells with an activated (CD62L-) phenotype persisted in blood of immunized mice for at least 2 mo, and exhibited decreased TCR and CD8 levels compared with their naive counterparts. In C57BL/6 mice, most M-MuLV-specific CD8+ CTL clones and immune PBL coexpressed V alpha3.2 in association with V beta5.2. Moreover, these V beta5.2+ V alpha3.2+ cells were shown to recognize the recently described H-2Db-restricted epitope (CCLCLTVFL) encoded in the leader sequence of the M-MuLV gag polyprotein. Collectively, our data demonstrate a highly restricted TCR repertoire in the CD8+ T cell response to M-MuLV-associated Ags in vivo, and suggest the potential utility of flow-microfluorometric analysis of V beta and V alpha expression in the diagnosis and monitoring of viral infections.
Animals, Antigens, Viral/administration & dosage, Antigens, Viral/immunology, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Clone Cells, Cytotoxicity, Immunologic, Down-Regulation/immunology, Epitopes, T-Lymphocyte/administration & dosage, Epitopes, T-Lymphocyte/immunology, Flow Cytometry, Gene Products, gag/immunology, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor/immunology, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/immunology, Immunization, Secondary, Immunodominant Epitopes/administration & dosage, Immunodominant Epitopes/immunology, Injections, Intraperitoneal, Kinetics, Leukemia, Experimental, Lymphocyte Culture Test, Mixed, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Moloney murine leukemia virus/immunology, Neoplasm Transplantation, Receptors, Antigen, T-Cell, alpha-beta/genetics, Receptors, Antigen, T-Cell, alpha-beta/immunology, Retroviridae Infections, T-Lymphocytes, Cytotoxic/immunology, T-Lymphocytes, Cytotoxic/metabolism, Tumor Virus Infections
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