Role for lysosomal phospholipase A2 in iNKT cell-mediated CD1d recognition

被引：31

作者：

Paduraru, Crina ^{[1
,2
]}

Bezbradica, Jelena S. ^{[1
,2
]}

Kunte, Amit ^{[2
,3
]}

Kelly, Robert ^{[4
]}

Shayman, James A. ^{[4
]}

Veerapen, Natacha ^{[5
]}

Cox, Liam R. ^{[6
]}

Besra, Gurdyal S. ^{[5
]}

Cresswell, Peter ^{[1
,2
]}

机构：

[1] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA

[3] Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06520 USA

[4] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA

[5] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England

[6] Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 13期

基金：

英国惠康基金; 美国国家卫生研究院; 英国医学研究理事会;

关键词：

antigen processing; lipid storage disease; KILLER T-CELLS; TRIGLYCERIDE TRANSFER PROTEIN; NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; ANTIGEN PRESENTATION; 1-O-ACYLCERAMIDE SYNTHASE; NEGATIVE SELECTION; DENDRITIC CELLS; LIPID ANTIGEN; RECEPTOR;

D O I：

10.1073/pnas.1302923110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：5097 / 5102

页数：6

共 74 条

[1]

Lysosomal phospholipase A2 is selectively expressed in alveolar macrophages [J].