V-BETA-17 T-CELL DELETION BY ENDOGENOUS MAMMARY-TUMOR VIRUS IN WILD-TYPE-DERIVED MOUSE STRAIN

The wild-type-derived mouse strain PWK possesses a beta-chain variable region V(beta)17a2 allele, which is expressed on mature T cells as part of the T-cell receptor of most mice expressing I-E, whereas V(beta)17 T cells are deleted in all I-E+ laboratory mice bearing a V(beta)17a1 allele. However, (PWK X CBA/J)F1 progeny and the wild-type-derived mouse strain MAI, which possesses the V(beta)17a2 allele, display deletion of V(beta)17 T cells. Analysis of (PWK x CBA/J) x PWK and of (PWK x MAI) x PWK backcrosses demonstrates that endogenous mouse mammary tumor virus MTV-6 from CBA/J and a MTV from strain MAI control the clonal deletion of V(beta)17a2 as well as V(beta)3 T cells. Furthermore, among I-E- progeny of a (MAI x C57BL/6) X C57BL/6 backcross, we observed that mice inheriting MTV of MAI have a reduced level of V(beta)17 T cells, suggesting that the clonal deletion of V(beta)17a2 T cells can be mediated in the absence of the I-E molecule. The 3' long terminal repeat of MTV MAI was cloned and translation of the open reading frame was compared to those of MTV known to encode superantigens. Comparisons indicate that MTV MAI has significantly diverged from the other MTVs. However, MTV MAI and MTV-6 share a stretch of 11 identical amino acids at the C terminus, which is divergent in MTV reacting with other V(beta)s. This suggests that this region is involved in determining the specificity toward V(beta)s and has been selectively conserved through evolution of the Mus species.