Identification of Key Amino Acids of the Mouse Mammary Tumor Virus Superantigen Involved in the Specific Interaction with T-Cell Receptor V_βDomains

Abstract

Mouse mammary tumor virus (MMTV) is a retrovirus encoding a superantigen that is recognized in association with major histocompatibility complex class II by the variable region of the beta chain (V ␤ ) of the T-cell receptor. The C-terminal 30 to 40 amino acids of the superantigen of different MMTVs display high sequence variability that correlates with the recognition of particular T-cell receptor V ␤ chains. Interestingly, MMTV(SIM) and mtv-8 superantigens are highly homologous but have nonoverlapping T-cell receptor V ␤ specificities. To determine the importance of these few differences for specific V ␤ interaction, we studied superantigen responses in mice to chimeric and mutant MMTV(SIM) and mtv-8 superantigens expressed by recombinant vaccinia viruses. We show that only a few changes (two to six residues) within the C terminus are necessary to modify superantigen recognition by specific V ␤ s. Thus, the introduction of the MMTV(SIM) residues 314-315 into the mtv-8 superantigen greatly decreased its V ␤ 12 reactivity without gain of MMTV(SIM)-specific function. The introduction of MMTV(SIM)-specific residues 289 to 295, however, induced a recognition pattern that was a mixture of MMTV(SIM)-and mtv-8-specific V ␤ reactivities: both weak MMTV(SIM)-specific V ␤ 4 and full mtv-8-specific V ␤ 11 recognition were observed while V ␤ 12 interaction was lost. The combination of the two MMTV(SIM)-specific regions in the mtv-8 superantigen established normal MMTV(SIM)-specific V ␤ 4 reactivity and completely abolished mtv-8-specific V ␤ 5, -11, and -12 interactions. These new functional superantigens with mixed V ␤ recognition patterns allowed us to precisely delineate sites relevant for molecular interactions between the SIM or mtv-8 superantigen and the T-cell receptor V ␤ domain within the 30 C-terminal residues of the viral superantigen.

Prevalent de novo somatic mutations in superantigen genes of mouse mammary tumor viruses in the genome of C57BL/6J mice and its potential implication in the immune system

“…These C-terminus regions from different MMTV SAgs are highly polymorphic. A region within the C-terminus (amino acid positions 42-74; Figure 3C ) was determined to be important for TCR Vβ specificity, including binding affinity [ 32 , 33 ]. Among the 17 unique SAg isoforms, 13 SAgs had non-synonymous point mutations in this region in comparison to the reference SAgs.…”

Differential Regulation of Peripheral CD4+ T Cell Tolerance Induced by Deletion and TCR Revision

“…ϩ TCRs, and is unusual among superantigens in failing to drive significant levels of T cell proliferation in vitro (13,14). Mtv-8 is carried by most strains of laboratory mice, including C57BL/6 (B6), and as a result of methylation, its expression is weak (15) and limited to the lymphoid periphery (16,17).…”

Experimental Arthritis in the Rat Induced by the Superantigen Staphylococcal Enterotoxin A

“…ERVs can encode for envelope proteins (env) with superantigenic properties . Superantigens may activate T lymphocytes in an oligoclonal manner by binding to MHC class II molecules followed by interaction with the T cell receptor (TCR) or by binding directly to the V β ‐chains of the TCR . A single superantigen (SAg) can activate up to 20% of the T cell repertoire.…”