Baribaud F, Wirth S, Maillard I, Valsesia S, Acha-Orbea H, Diggelmann H
Institute of Microbiology, University of Lausanne, CH-1011 Lausanne, CH-1066 Epalinges, Switzerland.
J Virol. 2001 Aug;75(16):7453-61. doi: 10.1128/JVI.75.16.7453-7461.2001.
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(beta)) 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(beta) chains. Interestingly, MMTV(SIM) and mtv-8 superantigens are highly homologous but have nonoverlapping T-cell receptor V(beta) specificities. To determine the importance of these few differences for specific V(beta) 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(beta)s. Thus, the introduction of the MMTV(SIM) residues 314-315 into the mtv-8 superantigen greatly decreased its V(beta)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(beta) reactivities: both weak MMTV(SIM)-specific V(beta)4 and full mtv-8-specific V(beta)11 recognition were observed while V(beta)12 interaction was lost. The combination of the two MMTV(SIM)-specific regions in the mtv-8 superantigen established normal MMTV(SIM)-specific V(beta)4 reactivity and completely abolished mtv-8-specific V(beta)5, -11, and -12 interactions. These new functional superantigens with mixed V(beta) 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(beta) domain within the 30 C-terminal residues of the viral superantigen.
小鼠乳腺肿瘤病毒(MMTV)是一种逆转录病毒,编码一种超抗原,该超抗原可被T细胞受体β链(Vβ)可变区与主要组织相容性复合体II类结合识别。不同MMTV超抗原的C末端30至40个氨基酸显示出高度的序列变异性,这与特定T细胞受体Vβ链的识别相关。有趣的是,MMTV(SIM)和mtv - 8超抗原高度同源,但具有不重叠的T细胞受体Vβ特异性。为了确定这少数差异对特定Vβ相互作用的重要性,我们研究了小鼠对重组痘苗病毒表达的嵌合和突变MMTV(SIM)和mtv - 8超抗原的超抗原反应。我们表明,C末端仅需少数几个变化(2至6个残基)就能改变特定Vβ对超抗原的识别。因此,将MMTV(SIM)的314 - 315位残基引入mtv - 8超抗原中,大大降低了其Vβ12反应性,且未获得MMTV(SIM)特异性功能。然而,引入MMTV(SIM)特异性残基289至295,诱导出一种识别模式,该模式是MMTV(SIM)和mtv - 8特异性Vβ反应性的混合:既观察到弱的MMTV(SIM)特异性Vβ4反应,又观察到完全的mtv - 8特异性Vβ11反应,而Vβ12相互作用丧失。mtv - 8超抗原中两个MMTV(SIM)特异性区域的组合建立了正常的MMTV(SIM)特异性Vβ4反应性,并完全消除了mtv - 8特异性Vβ5、-11和-12相互作用。这些具有混合Vβ识别模式的新功能超抗原使我们能够精确描绘病毒超抗原C末端30个残基内与SIM或mtv - 8超抗原和T细胞受体Vβ结构域之间分子相互作用相关的位点。