Bee venom processes human skin lipids for presentation by CD1a.

Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells...

पूर्ण विवरण

ग्रंथसूची विवरण
मुख्य लेखकों: Bourgeois, E, Subramaniam, S, Cheng, T, De Jong, A, Layre, E, Ly, D, Salimi, M, Legaspi, A, Modlin, R, Salio, M, Cerundolo, V, Moody, D, Ogg, G
स्वरूप: Journal article
भाषा:English
प्रकाशित: Rockefeller University Press 2015
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author Bourgeois, E
Subramaniam, S
Cheng, T
De Jong, A
Layre, E
Ly, D
Salimi, M
Legaspi, A
Modlin, R
Salio, M
Cerundolo, V
Moody, D
Ogg, G
author_facet Bourgeois, E
Subramaniam, S
Cheng, T
De Jong, A
Layre, E
Ly, D
Salimi, M
Legaspi, A
Modlin, R
Salio, M
Cerundolo, V
Moody, D
Ogg, G
author_sort Bourgeois, E
collection OXFORD
description Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom–derived phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2. These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases. The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease.
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spelling oxford-uuid:4e0893a0-353f-4e1e-844c-140c23f900d42022-03-26T15:58:50ZBee venom processes human skin lipids for presentation by CD1a.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4e0893a0-353f-4e1e-844c-140c23f900d4EnglishSymplectic Elements at OxfordRockefeller University Press2015Bourgeois, ESubramaniam, SCheng, TDe Jong, ALayre, ELy, DSalimi, MLegaspi, AModlin, RSalio, MCerundolo, VMoody, DOgg, GVenoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom–derived phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2. These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases. The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease.
spellingShingle Bourgeois, E
Subramaniam, S
Cheng, T
De Jong, A
Layre, E
Ly, D
Salimi, M
Legaspi, A
Modlin, R
Salio, M
Cerundolo, V
Moody, D
Ogg, G
Bee venom processes human skin lipids for presentation by CD1a.
title Bee venom processes human skin lipids for presentation by CD1a.
title_full Bee venom processes human skin lipids for presentation by CD1a.
title_fullStr Bee venom processes human skin lipids for presentation by CD1a.
title_full_unstemmed Bee venom processes human skin lipids for presentation by CD1a.
title_short Bee venom processes human skin lipids for presentation by CD1a.
title_sort bee venom processes human skin lipids for presentation by cd1a
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