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

Document Type

Article

Publication Date

2001

Keywords

Antigen-Presentation, Antigen-Presenting-Cells, Antigens-Viral, Enterotoxins, Female, Histocompatibility-Antigens-Class-II, Male, Mammary-Neoplasms-Experimental, Mammary-Tumor-Viruses-Mouse, Mice, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Mice-Inbred-CBA, Mice-Knockout, Mice-Transgenic, Peptides, Retroviridae-Infections, Staphylococcus-aureus, Superantigens, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes, Tumor-Virus-Infections

First Page

2244

Last Page

2250

JAX Source

J Immunol 2001 Feb; 166(4):2244-50.

Grant

CA34196/CA/NCI, CA65795/CA/NCI

Abstract

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.

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