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 changes 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 presentation of v-Sag and, subsequently, the life cycle of the mouse mammary tumor virus (MMTV). T cells reactive to v-Sag were found in mice lacking DM molecules as well as in A(b)Ep-transgenic mice in which MHC class II binding grooves were predominantly occupied by an invariant chain fragment or Ealpha(52-68) peptide, respectively. APCs from the mutant mice failed to present v-Sag, as determined by the lack of Sag-specific T cell activation, Sag-induced T cell deletion, and by the aborted MMTV infection. In contrast, mice that express I-A(b) with a variety of bound peptides presented v-Sag and were susceptible to MMTV infection. Comparison of v-Sag and b-Sag presentation by the same mutant cells suggested that presentation of v-Sag had requirements 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.
Golovkina
T
T
The Jackson Laboratory, Bar Harbor, ME 04609, USA. tvg@aretha.jax.org
Agafonova
Y
Y
Kazansky
D
D
Chervonsky
A
A
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism*; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D004768:Enterotoxins; C416189:H2-M antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010455:Peptides; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal