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首页> 外文期刊>Infection and immunity >Superantigenic properties of the group A streptococcal exotoxin SpeF (MF).
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Superantigenic properties of the group A streptococcal exotoxin SpeF (MF).

机译：A组链球菌外毒素SpeF（MF）的超抗原特性。

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Streptococcal pyrogenic exotoxin F (SpeF), previously referred to as mitogenic factor, is a newly described potent mitogen produced by group A streptococci. To investigate whether this protein belongs to the family of microbial superantigens, we analyzed the cellular and molecular requirements for its presentation to T cells and compared it with the known streptococcal superantigen pyrogenic exotoxin A (SpeA) and the nonspecific polyclonal T-cell mitogen phytohemagglutinin (PHA). SpeF and SpeA were efficiently presented by autologous antigen-presenting cells (APCs) and an allogeneic B lymphoma cell line, Raji. In contrast, the monocytic cell line U937, which does not express major histocompatibility complex (MHC) class II molecules, failed to present SpeF as well as SpeA but supported the response to PHA. Thus, the presentation of SpeF by APCs was class II dependent but not MHC restricted. The requirement for HLA class II was further supported by the ability of anti-HLA-DQ monoclonal antibody to block the SpeF-induced proliferative response by 75 to 100%. Paraformaldehyde (PFA) fixation of autologous APCs resulted in an impaired ability of SpeF and SpeA to induce optimal T-cell proliferation. In contrast, fixation of Raji cells did not affect the induced proliferation. The stimulatory effect of PHA remained unaffected by both the use of PFA-fixed APCs and the addition of the HLA class II-specific monoclonal antibodies. The addition of a supernatant enriched in interleukin 1 and interleukin 6 to fixed autologous APCs resulted in an increased SpeF-induced response; thus, the impairment was not due to a requirement for processing, but, rather, costimulatory factors produced by metabolically active APCs were needed. SpeF was found to preferentially activate T cells bearing V beta 2, 4, 8, 15, and 19, as determined by quantitative PCR. The data presented clearly show that SpeF is a superantigen. We also studied the prevalence of the speF gene in clinical isolates by Southern blot analyses, and the gene could be detected in 42 group A streptococcal strains, which represented 14 serotypes.
机译：链球菌热原性外毒素F（SpeF），以前称为有丝分裂因子，是A组链球菌产生的一种新描述的强有丝分裂原。为了研究这种蛋白质是否属于微生物超抗原家族，我们分析了将其呈递给T细胞的细胞和分子要求，并将其与已知的链球菌超抗原热原性外毒素A（SpeA）和非特异性多克隆T细胞促细胞分裂素植物血凝素（ PHA）。 SpeF和SpeA由自体抗原呈递细胞（APC）和同种异体B淋巴瘤细胞系Raji有效呈递。相比之下，不表达主要组织相容性复合体（MHC）II类分子的单核细胞系U937，不能同时呈现SpeF和SpeA，但支持对PHA的应答。因此，APC对SpeF的呈递依赖于II类，但不受MHC限制。抗HLA-DQ单克隆抗体将SpeF诱导​​的增殖反应阻滞75％至100％的能力进一步支持了对HLA II类的需求。自体APC的低聚甲醛（PFA）固定导致SpeF和SpeA诱导最佳T细胞增殖的能力受损。相反，Raji细胞的固定并不影响诱导的增殖。使用PFA固定的APC和添加HLA II类特异性单克隆抗体均不会影响PHA的刺激作用。向固定的自体APC中添加富含白介素1和白介素6的上清液，会导致SpeF诱导​​的反应增加。因此，损伤不是由于需要加工而引起的，而是需要代谢活跃的APC产生的共刺激因子。通过定量PCR确定，发现SpeF优先激活带有V beta 2、4、8、15和19的T细胞。呈现的数据清楚地表明SpeF是一种超级抗原。我们还通过Southern印迹分析研究了speF基因在临床分离株中的流行情况，该基因可以在代表14种血清型的42个A组链球菌菌株中检​​测到。

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