Hierarchal Utilization of Different T-Cell Receptor Vβ Gene Segments in the CD8(+)-T-Cell Response to an Immunodominant Moloney Leukemia Virus-Encoded Epitope In Vivo

The CD8(+)-T-cell response to Moloney murine leukemia virus (M-MuLV)-associated antigens in C57BL/6 mice is directed against an immunodominant gag-encoded epitope (CCLCLTVFL) presented in the context of H-2D(b) and is restricted primarily to cytotoxic T lymphocytes (CTL) expressing the Vα3.2 and Vβ5.2 gene segments. We decided to examine the M-MuLV response in congenic C57BL/6 Vβ(a) mice which are unable to express the dominant Vα3.2(+) Vβ5.2(+) T-cell receptor (TCR) due to a large deletion at the TCR locus that includes the Vβ5.2 gene segment. Interestingly, M-MuLV-immune C57BL/6 Vβ(a) mice were still able to reject M-MuLV-infected tumor cells and direct ex vivo analysis of peripheral blood lymphocytes from these immune mice revealed a dramatic increase in CD8(+) cells utilizing the same Vα3.2 gene segment in association with two different Vβ segments (Vβ3 and Vβ17). Surprisingly, all these CTL recognized the same immunodominant M-MuLV gag epitope. Analysis of the TCR repertoire of individual M-MuLV-immune (C57BL/6 × C57BL/6 Vβ(a))F(1) mice revealed a clear hierarchy in Vβ utilization, with a preferential usage of the Vβ17 gene segment, whereas Vβ3 and especially Vβ5.2 were used to much lesser extents. Sequencing of TCRα- and -β-chain junctional regions of CTL clones specific for the M-MuLV gag epitope revealed a diverse repertoire of TCRβ chains in Vβ(a) mice and a highly restricted TCRβ-chain repertoire in Vβ(b) mice, whereas TCRα-chain sequences were highly conserved in both cases. Collectively, our data indicate that the H-2D(b)-restricted M-MuLV gag epitope can be recognized in a hierarchal fashion by different Vβ domains and that the degree of β-chain diversity varies according to Vβ utilization.