Pairing of V beta 6 with certain V alpha 2 family members prevents T cell deletion by Mtv-7 superantigen

Superantigens (SAg) are proteins of bacterial or viral origin able to activ ate T cells by forming a trimolecular complex with both MHC class II molecu les and the T cell receptor (TCR), leading to clonal deletion of reactive T cells in the thymus. SAg interact with the TCR through the beta chain vari able region (V beta), but the TCR alpha chain has been shown to have an inf luence on the T cell reactivity. We have investigated here the role of the TCR alpha chain in the modulation of T cell reactivity to Mtv-7 SAg by comp aring the peripheral usage of V alpha2 in V beta6(+) (SAg-reactive) and V b eta8.2(+) (SAg non-reactive) T cells, in either BALB/D2 (Mtv-7(+)) or BALB/ c (Mtv-7(+)) mice. The results show, first, that pairing of V beta6 with ce rtain V alpha2 family members prevents T cell deletion by Mtv-7 SAg. Second , there is a strikingly different distribution of the V alpha2 family membe rs in CD4 and CD8 populations of V beta6 but not of V beta8.2 T cells, irre spective of the presence of Mtv-7 SAg. Third, the alpha chain may play a ro le in the overall stability of the TCR/SAg/MHC complex. Taken together, the se results suggest that the V alpha domain contributes to the selective pro cess by its role in the TCR reactivity to SAg:MHC class II complexes, most likely by influencing the orientation of the V beta domain in the TCR alpha beta heterodimer. (C) 2001 Elsevier Science Ltd. All rights reserved.