Immunogenic Properties of Lipid A

Galanos, Chris; Freudenberg, Marina A.; Jay, Frances; Nerkar, D. P.; Veleva, K.; Brade, Helmut; Strittmatter, Wolfgang

doi:10.1093/clinids/6.4.546

Cited by 82 publications

(39 citation statements)

References 19 publications

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“…Also, most preparations were antigenically active. This would be expected because it had already been established that for the expression of lipid A antigenicity the presence of ester-linked fatty acids and phosphate are not necessary [21].…”

Section: Discussionmentioning

confidence: 99%

Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities

Galanos¹,

Lüderitz²,

Rietschel³

et al. 1985

European Journal of Biochemistry

452

258

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The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the following test systems: lethal toxicity, pyrogenicity, local Shwartzman reactivity, Limulus amoebocyte lysate gelation capacity, tumour necrotizing activity, B cell mitogenicity, induction of prostaglandin synthesis in macrophages, and antigenic specificity. It was found that synthetic and natural free lipid A exhibit identical activities and are indistinguishable in all tests.Lipopolysaccharides (endotoxins) of gram-negative bacteria which consist of a heteropolysaccharide and a lipid component (termed lipid A) elicit multiple acute pathophysiological effects such as fever, lethality, Shwartzman reactivity, macrophage and B-lymphocyte activation, and other activities [I]. In 1954 it was proposed that for the induction of these effects the polysaccharide portion is dispensable and that the lipid A component represents the active center responsible for the endotoxic properties of lipopolysaccharides [2]. Evidence for this was then obtained in numerous investigations [2 -41 and this concept is now generally accepted.The chemical structure of the lipid A component of several enterobacterial lipopolysaccharides has been analysed during recent years in great detail (for reviews see [5, 61) and it was recognized that lipid A of Escherichiu coli possesses a comparatively simple structure. Free E. coli lipid A consists of a 8(1-6)-linked D-glucosamine disaccharide which is substituted by two phosphoryl groups, one being bound to position 4' of the nonreducing glucosamine residue (GlcN 11) and one being a-linked [7] to the glycosidic hydroxyl group of the reducing glucosaminyl group (GlcN I) (Fig.

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Section: Discussionmentioning

confidence: 99%

Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities

Galanos¹,

Lüderitz²,

Rietschel³

et al. 1985

European Journal of Biochemistry

452

258

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“…From binding assay data (table 11), the binding site of most of the antibodies examined in the present study could be localised precisely: antibody from cell lines 2,3,4,5,8,9,11 and 13 bound to LPS from strains J5 and R5 (both Rc chemotypes), but not to LPS from S. minnesota strains R595 (chemotype Re), R7 (chemotype Rdl), R345 (chemotype Rbz) or R60 (chemotype Ra), nor to Lipid A. From a review of the molecular structures of these core antigens (Galanos et al, 1984) it can be stated that all these antibodies bind to the terminal glucose residue present in the Rc structure, i.e., this glucose residue is an immunodominant group. Immunodominance of the terminal, non-reducing sugar is common when rough strains are used as immunogens (Galanos et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

“…From a review of the molecular structures of these core antigens (Galanos et al, 1984) it can be stated that all these antibodies bind to the terminal glucose residue present in the Rc structure, i.e., this glucose residue is an immunodominant group. Immunodominance of the terminal, non-reducing sugar is common when rough strains are used as immunogens (Galanos et al, 1984). Considering the ratio of their titres to LPS from strains J5 and R5, the antibodies can be divided into three groups, each recognising a different epitope on the terminal glucose residue : (i) a group characterised by a ratio of 1: 1, exemplified by antibody from cell lines 3, 8, 9, 11 and 13 ; (ii) a group with a ratio of 10 : 1, including antibody from cell lines 4 and 5; and (iii) a group with a ratio of 100: 1, containing antibody from cell line 2.…”

Section: Discussionmentioning

confidence: 99%

Production and characterisation of mouse monoclonal antibodies reacting with the lipopolysaccharide core region of gram-negative bacilli

Appelmelk

Vught

Maaskant

et al. 1988

Journal of Medical Microbiology

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Summary.Monoclonal anti bodies to the lipopolysaccharide (LPS) core region were produced by immunising mice with Escherichia coli strain J5 (chemotype Rc). One of these bound to the deepest part of the core, i.e., Lipid A, and reacted with other heatkilled but not live gram-negative bacilli, including E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Eight other monoclonal antibodies, binding to the terminal glucose residue of Rc LPS, reacted with live cells of E. coli strains only. Thus, the 0 antigen does not necessarily render the core inaccessible to antibody. However, despite binding to live bacteria, these monoclonal antibodies neither enhanced phagocytic killing, nor protected mice from dying from gram-negative infection or endotoxaemia. It is concluded that antibodies reacting with the most immunodominant parts of the J5 core are not protective.

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“…LPS hydrolysis (23). 1 mg of purified smooth LPS was mixed with 3 ml of 1% acetic acid in a I0-ml capacity round-bottom flask.…”

Section: Methodsmentioning

confidence: 99%

Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of lipopolysaccharides.

Pollack¹,

Raubitschek²,

Larrick³

1987

J. Clin. Invest.

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Immunogenic Properties of Lipid A

Cited by 82 publications

References 19 publications

Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities

Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities

Production and characterisation of mouse monoclonal antibodies reacting with the lipopolysaccharide core region of gram-negative bacilli

Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of lipopolysaccharides.

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