Expression of V beta (beta-chain variable region) gene segments was investigated in the Mus m. domesticus DDO strain, which possesses a large genomic deletion encompassing 20 of the 29 V beta gene segments known in BALB/c. Stainings using V beta-specific monoclonal antibodies revealed that up to 60% of the peripheral T cells use 3 V beta gene segments. Variable frequencies of V beta 2 T cells were observed among DDO individuals. Segregation analyses of F2 crosses between V beta 2-deletor mice and mammary tumor virus (Mtv)-free mice led to the identification of a new endogenous Mtv, named Mtv-DDO, mediating V beta 2 T cell clonal deletion. Mtv-DDO structure is conserved with the exception of the carboxy-terminal region as compared to other Mtv. Comparison between Mtv sharing the same V beta specificity and isolated from laboratory or wild mice confirms that a stretch of 11 amino acids, defined as the V beta-specific region, is required for the V beta-specific interaction. Limited substitutions in this region account for the shift of the Mtv specificity towards different V beta.