Vβ7CD4 T-cell levels predict HERV-K18 SAg reactivity. To causally relate peripheral T-cell levels with SAg reactivity, we first established a link between intrathymic and peripheral Vβ7CD4 cell levels and subsequently with SAg reactivity. (A) The thymic CD4/CD8 ratios of Vβ2, Vβ7, and Vβ17 were determined on CD1A^- thymocytes of 7 donors. (B) For 3 donors, the thymic and peripheral T-cell Vβ-CD4/CD8 ratios were compared. (C) Forty-seven healthy donors were divided in 2 groups of similar age and with Vβ7^CD4/_CD8 ratios less than and 0.5, respectively. The Vβ7 percentages among CD4⁺ T cells were determined by FACS. For 19 other controls, Vβ families were also analyzed. (D) Expansions of Vβ7CD4 T cells from 16 donors with high or low proportions of SAg-reactive Vβ7CD4 T cells were analyzed. T cells from 8 donors with Vβ7^CD4/_CD8 ratios greater than 0.5 and from 8 with ratios less than 0.5 were analyzed after culture with vector and SAg-transfected A20 cells. For 8 donors, the control family Vβ2 was also determined. Differential reactivity was corroborated for another 14 donors (not shown). ▴ represent individual values; horizontal bars represent the mean.