Bavari S, Ulrich R G
Department of Immunology and Molecular Biology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011.
Infect Immun. 1995 Feb;63(2):423-9. doi: 10.1128/iai.63.2.423-429.1995.
We have examined the role of the CD4 molecule in primary T-lymphocyte responses to the staphylococcal enterotoxins SEA, SEB, SEC1, and the toxic shock syndrome toxin TSST-1. Proliferating cells were predominantly CD4+; however, the responses to SEA and TSST-1 were most sensitive to inhibition by the anti-CD4 antibody Leu-3a. T-lymphocyte responses to the bacterial superantigens were inhibited by site-directed mutations of residues in the DR beta membrane-proximal domain (DR beta 2) that are also known to be important for interactions with CD4. SEA and TSST-1 binding to DR was reduced by the DR beta 2 mutations and by competition with soluble recombinant CD4. We propose that bacterial superantigens sequentially, or simultaneously with CD4, stabilize complexes of T-cell antigen receptors and major histocompatibility complex class II molecules. The superantigen qualities of these toxins may be due, in part, to a molecular mimicry of CD4 and other adhesion molecules.
我们研究了CD4分子在原发性T淋巴细胞对葡萄球菌肠毒素SEA、SEB、SEC1以及中毒性休克综合征毒素TSST-1反应中的作用。增殖细胞主要为CD4⁺；然而，对SEA和TSST-1的反应对抗CD4抗体Leu-3a的抑制最为敏感。T淋巴细胞对细菌超抗原的反应受到DRβ膜近端结构域（DRβ2）中残基的定点突变抑制，这些残基已知对与CD4的相互作用也很重要。DRβ2突变以及与可溶性重组CD4的竞争降低了SEA和TSST-1与DR的结合。我们提出，细菌超抗原依次或与CD4同时稳定T细胞抗原受体和主要组织相容性复合体II类分子的复合物。这些毒素的超抗原特性可能部分归因于对CD4和其他黏附分子的分子模拟。
