Diverse repertoire of the MHC class II-peptide complexes is required for presentation of viral superantigens

Among other features, peptides affect MHC class II molecules, causing chang es in the binding of bacterial superantigens (b-Sag), Whether peptides can alter binding of viral superantigens (v-Sag) to MHC class II was not known. Here we addressed the question of whether mutations limiting the diversity of peptides bound by the MHC class II molecules influenced the presentatio n of v-Sag and, subsequently; the life cycle of the mouse mammary tumor vir us (MMTV). T cells reactive to v-Sag were found in mice lacking DM molecule s as well as in A(b)Ep-transgenic mice in which MHC class II binding groove s were predominantly occupied by an invariant chain fragment or E alpha (52 -68) peptide, respectively, APCs from the mutant mice failed to present v-S ag, as determined by the lack of Sag-specific T cell activation, Sag-induce d T cell deletion, and by the aborted MMTV infection. In contrast, mice tha t express I-A(b) with a variety of hound peptides presented v-Sag and were susceptible to MMTV infection. Comparison of v-Sag and b-Sag presentation b y the same mutant cells suggested that presentation of v-Sag had requiremen ts similar to that for presentation of toxic shock syndrome toxin-1. Thus, MHC class II peptide repertoire is critical for recognition of v-Sag by the T cells and affects the outcome of infection with a retrovirus.