The Type B Leukemogenic Virus Truncated Superantigen Is Dispensable for T-Cell Lymphomagenesis

Mouse mammary tumor virus (MMTV) is a slow-acting oncogenic retrovirus that causes mammary tumors in mice after a long period (6 to 9 months) (1, 29). An MMTV variant, type B leukemogenic virus (TBLV), has been demonstrated to cause thymic lymphomas with a short latency period (1.5 to 2 months) when injected intrathymically into neonatal mice (2). Compared to MMTV, TBLV has a deletion of 443 nucleotides and a substitution of 124 nucleotides in the U3 region of the long terminal repeat (LTR) (3). This deletion removes a negative regulatory element (NRE) present in the MMTV LTR (17-19, 23, 36, 37), which has been implicated in tissue-specific MMTV expression (6, 30). The substitution creates a triplication of a 62-bp element comprised of sequences flanking the deletion (3) (Fig. ​(Fig.1A1A). FIG. 1. Construction and characterization of hybrid MMTV-TBLV proviral clones. (A) Diagram of parental and hybrid MMTV clones. The pHYB-MTV plasmid contains a hybrid between Mtv1 and C3H MMTV. A white box indicates the region upstream of the EcoRI site that is ... The LTR deletion and substitution also truncate the open reading frame (ORF) encompassing the U3 region of the LTR (Fig. ​(Fig.1A).1A). This ORF encodes a 37-kDa, type II transmembrane glycoprotein known as superantigen (Sag) that functions in the milk-borne transmission of MMTV (1, 7, 9, 10, 16) by the stimulation of T cells through the T-cell receptor (TCR) (33, 35). The truncated Sag protein encoded in the TBLV LTR lacks the entire C-terminal region that interacts with the TCR, yet it retains the transmembrane region, a part of the extracellular region that includes the five glycosylation sites, a single proteolytic processing site, and the major histocompatibility complex class II protein binding motif (12, 20). This study shows that the truncated TBLV Sag protein is dispensable for virally induced T-cell lymphomas.