DIFFERENTIAL REACTIVITY OF TCR V-BETA-10 ALLELES TO A MOUSE MAMMARY-TUMOR VIRUS SUPERANTIGEN

Mouse mammary tumor virus (MMTV) expresses a superantigen (SAg) which plays a critical role in the viral life cycle. We have recently descri bed the new infectious MMN (SIM) encoding a V beta 4-specific SAg in m ice with a TCR-V beta(b) haplotype. We have now compared the SAg activ ity of this virus in BALB/c mice harboring the TCR-V beta(a), TCR-V be ta(b) or TCR-V beta(c) haplotypes which differ by a central deletion i n the TCR-V beta(a) and TCR-V beta(c) locus and by mutations in some o f the remaining V beta elements. Injection of MMTV (SIM) led to a stro ng stimulation of V beta 4+ CD4+ T cells in TCR-V beta(b) mice, but on ly to a weak stimulation of these cells in TCR-V beta(a) or TCR-V beta (c) mice. A large increase in the percentage of V beta 10+ cells was o bserved among CD4+ T cells in mice with the V beta(a) or V beta(c), bu t not the V beta(b) TCR-V beta haplotype. V beta 10+ cells dominated t he response when V beta 10(a/c) and V beta 4 subsets were present toge ther. This is the first report of a viral SAg interacting with murine V beta 10+ cells. Six amino acid differences between V beta 10(a/c) an d V beta 10(b) could account for the gain of reactivity of V beta 10(a /c) to the MMTV(SIM) SAg. No mutations were found in the hypervariable region 4 (HV4) of the TCR. Mutations at positions 22 and 28 introduce into V beta 10(a/c) the same amino acids which are found at these pos itions in the MMN(SIM)-reactive V beta 4. Tridimensional models indica ted that these amino acids lie close to HV4 and are likely to be impor tant for the interaction of the SAg with the TCR.