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The Biology of NKT Cells Albert Bendelac - part 2

Làm thế nào quản lý ngoại sinh hoặc chất béo trong tế bào nội sinh chọn giữa những con đường và hậu quả để trình bày kháng nguyên là những câu hỏi mà chỉ mới bắt đầu được giải quyết và có thể phụ thuộc vào tính chất nội tại chẳng hạn như chiều dài hoặc insaturation chuỗi alky | Annu. Rev. Immunol. 2007.25 297-336. Downloaded from arjournals.annualreviews.org by HINARI on 09 21 07. For personal use only. pathways overlap only partially with those governing the trafficking of endogenous glycosphingolipids which are synthesized in the lumenal part of the Golgi and thought to reach the plasma membrane first then the endosome through clathrin-dependent and -independent endocytosis until they are degraded in the lysosome 103 . How exogenously administered or endogenous intracellular lipids choose between these pathways and the consequence for antigen presentation are questions that are just beginning to be addressed and may depend on intrinsic properties such as length or insaturation of alkyl chains 104 composition of the polar head and solubility in aqueous environments as well as extrinsic variations in the mode of administration such as use of detergents liposomes or lipid-protein complexes. The development of new methodologies genetic manipulation and reagents will be required to address these essential questions. In addition recognition of microbial lipids in the context of infection most likely involves different pathways because the uptake of bacteria is governed by different sets of cell surface receptors and the release of cell wall lipids would occur through degradation of the microorganism in the lysosome before processing and loading onto CD1d. Lipid Exchange Proteins Although an intrinsic pH-dependent mechanism appears to favor the acquisition of some lipids by CD1 proteins perhaps through a conformational change 105 106 lipid exchange now appears to be regulated by specialized lipid transfer proteins. By using various detergents early studies of lipid binding to CD1 molecules tacitly dealt with the fact that in general lipids are insoluble in water forming micelles that cannot transfer monomeric lipids onto CD1. These detergents however also tended to dislodge lipids bound to CD1 as shown directly in the crystal structure of CD1b