Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520-8011, USA.
Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5097-102. doi: 10.1073/pnas.1302923110. Epub 2013 Mar 14.
Invariant natural killer T (iNKT) cells recognize self lipid antigens presented by CD1d molecules. The nature of the self-antigens involved in the development and maturation of iNKT cells is poorly defined. Lysophospholipids are self-antigens presented by CD1d that are generated through the action of phospholipases A1 and A2. Lysosomal phospholipase A2 (LPLA2, group XV phospholipase A2) resides in the endocytic system, the main site where CD1d antigen acquisition occurs, suggesting that it could be particularly important in CD1d function. We find that Lpla2(-/-) mice show a decrease in iNKT cell numbers that is neither the result of a general effect on the development of lymphocyte populations nor of effects on CD1d expression. However, endogenous lipid antigen presentation by CD1d is reduced in the absence of LPLA2. Our data suggest that LPLA2 plays a role in the generation of CD1d complexes with thymic lipids required for the normal selection and maturation of iNKT cells.
不变自然杀伤 T(iNKT)细胞识别由 CD1d 分子呈递的自身脂质抗原。涉及 iNKT 细胞发育和成熟的自身抗原的性质尚未明确。溶血磷脂是由磷脂酶 A1 和 A2 的作用产生的由 CD1d 呈递的自身抗原。溶酶体磷脂酶 A2（LPLA2，XIV 组磷脂酶 A2）位于内吞系统中，这是 CD1d 抗原摄取发生的主要部位，表明它可能在 CD1d 功能中特别重要。我们发现 Lpla2(-/-) 小鼠的 iNKT 细胞数量减少，这既不是对淋巴细胞群发育的普遍影响的结果，也不是对 CD1d 表达的影响的结果。然而，在没有 LPLA2 的情况下，CD1d 对内源性脂质抗原的呈递减少。我们的数据表明，LPLA2 在生成与胸腺脂质结合的 CD1d 复合物中发挥作用，这些复合物对于 iNKT 细胞的正常选择和成熟是必需的。
