Ernst W A, Maher J, Cho S, Niazi K R, Chatterjee D, Moody D B, Besra G S, Watanabe Y, Jensen P E, Porcelli S A, Kronenberg M, Modlin R L
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095, USA.
Immunity. 1998 Mar;8(3):331-40. doi: 10.1016/s1074-7613(00)80538-5.
The ability of human CD1b molecules to present nonpeptide antigens is suggested by the T cell recognition of microbial lipids and lipoglycans in the presence of CD1b-expressing antigen-presenting cells. We demonstrate the high-affinity interaction of CD1b molecules with the acyl side chains of known T cell antigens, lipoarabinomannan, phosphatidylinositol mannoside, and glucose monomycolate. Furthermore, CD1b-antigen binding was optimal at acidic pH, consistent with the known requirement for endosomal acidification in CD1b-restricted antigen presentation. The mechanism for CD1b-ligand interaction involves the partial unfolding of the alpha helices of CD1b at acidic pH, revealing a hydrophobic binding site that could accommodate lipid. These data provide direct evidence that the CD1b molecule has evolved unique biochemical properties that enable the binding of lipid-containing antigens from intracellular pathogens.
在表达CD1b的抗原呈递细胞存在的情况下，T细胞对微生物脂质和脂多糖的识别表明人类CD1b分子具有呈递非肽抗原的能力。我们证明了CD1b分子与已知T细胞抗原脂阿拉伯甘露聚糖、磷脂酰肌醇甘露糖苷和单霉菌酸葡萄糖的酰基侧链之间存在高亲和力相互作用。此外，CD1b与抗原的结合在酸性pH条件下最为理想，这与CD1b限制性抗原呈递中内体酸化的已知要求一致。CD1b与配体相互作用的机制涉及CD1b的α螺旋在酸性pH条件下部分展开，暴露出一个可容纳脂质的疏水结合位点。这些数据提供了直接证据，表明CD1b分子进化出了独特的生化特性，使其能够结合来自细胞内病原体的含脂质抗原。
