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TLR4 interacts with lipopolysaccharide’s component lipid A, structure of which highly influences the recognition. TLR4 activation results in expression of proinflammatory cytokines. We measured biological activity of various lipid A from LPS preparations isolated from number of pathogens. We have shown that number and length of lipid chains in lipid A correlates directly with ability to activate production of proinflammatory cytokines by BMDM. We decided to establish which amino acids of TLR4 are involved in interaction with phosphates of lipid A. To this point, we generated a number of TLR4 point mutants and started to test their biological activity.