Quantitation of CD8(+) T-lymphocyte responses to multiple epitopes from simian virus 40 (SV40) large T antigen in C57BL/6 mice immunized with SV40, SV40 T-antigen-transformed cells, or vaccinia virus recombinants expressing full-length T antigen or epitope minigenes.

Mylin LM, Schell TD, Roberts D, Epler M, Boesteanu A, Collins EJ, Frelinger JA, Joyce S, Tevethia SS
J Virol. 2000 74 (15): 6922-34

PMID: 10888631 · PMCID: PMC112209 · DOI:10.1128/jvi.74.15.6922-6934.2000

The cytotoxic T-lymphocyte response to wild-type simian virus 40 large tumor antigen (Tag) in C57BL/6 (H2(b)) mice is directed against three H2-D(b)-restricted epitopes, I, II/III, and V, and one H2-K(b)-restricted epitope, IV. Epitopes I, II/III, and IV are immunodominant, while epitope V is immunorecessive. We investigated whether this hierarchical response was established in vivo or was due to differential expansion in vitro by using direct enumeration of CD8(+) T lymphocytes with Tag epitope/major histocompatibility complex class I tetramers and intracellular gamma interferon staining. The results demonstrate that epitope IV-specific CD8(+) T cells dominated the Tag-specific response in vivo following immunization with full-length Tag while CD8(+) T cells specific for epitopes I and II/III were detected at less than one-third of this level. The immunorecessive nature of epitope V was apparent in vivo, since epitope V-specific CD8(+) T cells were undetectable following immunization with full-length Tag. In contrast, high levels of epitope V-specific CD8(+) T lymphocytes were recruited in vivo following immunization and boosting with a Tag variant in which epitopes I, II/III, and IV had been inactivated. In addition, analysis of the T-cell receptor beta (TCRbeta) repertoire of Tag epitope-specific CD8(+) cells revealed that multiple TCRbeta variable regions were utilized for each epitope except Tag epitope II/III, which was limited to TCRbeta10 usage. These results indicate that the hierarchy of Tag epitope-specific CD8(+) T-cell responses is established in vivo.

MeSH Terms (18)

Animals Antibodies Antigens, Polyomavirus Transforming CD8-Positive T-Lymphocytes Cell Line, Transformed Cell Transformation, Viral Epitopes, T-Lymphocyte Female Histocompatibility Antigens Class I Immunization Interferon-gamma Male Mice Mice, Inbred C57BL Receptors, Antigen, T-Cell, alpha-beta Recombinant Proteins Simian virus 40 Vaccinia virus

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