Optimizing NKT Cell Ligands as Vaccine Adjuvants

Carreño, Leandro J.; Kharkwal, Shalu Sharma; Porcelli, Steven A.

doi:10.2217/imt.13.175

Cited by 76 publications

(76 citation statements)

References 112 publications

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“…Even more, other unconventional T cell subsets may drive similar reactions, albeit in response to different stimuli and in different anatomical contexts, arguing for a general role of innate T cell subsets as natural adjuvants to promote protective immune responses. In analogy to the exploitation of iNKT cells in the clinic [193][194][195]223,224], approaches specifically targeting Vc9/Vd2 T cells may have a similar potential as vaccine adjuvant, to boost immune responses against pathogens and tumors and to modulate autoimmune responses.…”

Section: Innate Regulation Of Adaptive Immune Responses: Vd2 + Versusmentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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Section: Innate Regulation Of Adaptive Immune Responses: Vd2 + Versusmentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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“…El azúcar en unión α es una característica importante puesto que las células de mamífero solo pueden sintetizar glicolípidos con unión β-anomérica, y esta última es muy poco estimuladora de las iNKT (5). A partir de este compuesto se han sintetizado múltiples análogos con modificaciones principalmente en el azúcar y en las colas lipídicas; el azúcar que sobresale de la molécula CD1d es uno de los principales determinantes en el reconocimiento y afinidad del TCR (6,8,26) (tabla 1).…”

Section: Antígenos Lipídicos Sintéticosunclassified

“…Un compuesto similar a este último es el llamado HS44, en el que adicionalmente se sustituye el oxígeno de unión al azúcar por un grupo amino y produce una menor respuesta de IFN-γ in vitro, pero niveles comparables in vivo con respecto a αGalCer (29). Recientemente se describió un análogo llamado 7DW8-5 (tabla 1) que ha mostrado tener una actividad mayor como adyuvante en malaria y VIH, comparado con KRN7000 (6,30).…”

Section: Antígenos Lipídicos Sintéticosunclassified

“…Las células iNKT se caracterizan por la expresión del factor zinc-promielocítico de leucemia (PLZF, codificado por Zbtb16), que es inducido durante el desarrollo tímico y permite la adquisición de un programa efector innato (1). Tal programa confiere a las iNKT la capacidad de producir citocinas tanto proinflamatorias como antinflamatorias (3,(4)(5)(6)(7).…”

Section: Introductionunclassified

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Mecanismos de activación de las células T asesinas naturales invariantes (iNKT)

Baena

Gómez-Giraldo

Carreño

2015

iatreia

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RESUMENAunque se ha logrado un conocimiento amplio acerca de las células T asesinas naturales (iNKT), aún no existe consenso sobre sus mecanismos de activación. Dichas células reconocen diferentes antígenos glicolipídicos presentados por medio de la molécula CD1d, los cuales pueden ser endógenos, exógenos derivados de organismos como bacterias y sintéticos desarrollados para aplicaciones clínicas. Existe mucho interés en entender cómo estas distintas variantes glicolipídicas inducen diferentes tipos de polarización, pero ha sido muy difícil llegar a un consenso, debido a que la respuesta depende de varios factores como la naturaleza, la internalización y el procesamiento de los glicolípidos. Además, la activación de las células iNKT la determinan el tipo y estado de activación de la célula presentadora de antígeno, las moléculas coestimuladoras, los mecanismos de transactivación y la localización de los complejos CD1d-glicolípido en distintas microrregiones de la membrana plasmática, como las balsas lipídicas. Esta revisión explora la evidencia sobre los factores que afectan la activación de las células iNKT con el fin de entender su potencial inmunomodulador. PALABRAS CLAVEα-Galactosilceramida; Células Inkt; CD1d; Glicolípidos; Presentación Antigénica; TCR SUMMARY Activation mechanisms of invariant natural killer T cells (iNKTs)A great amount of knowledge on natural killer T cells (iNKTs) is now available, but a consensus about their activation mechanisms has not been reached. These cells recognize different glycolipid antigens through the CD1d molecule. Such antigens may be endogenous, derived from

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“…iNkt cells can secrete a large variety of cytokines to different glycolipid antigens presented by the CD1d molecule, which have been showed to influence the immune response in multiple infection diseases. In recent years different new glycolipid antigens has been identified, many of which have the potential to generate adjuvant effects that enhance the activity of adaptive immune cells such as dendritic cells (DCs), t cells and B cells (3,4). Moreover, for certain diseases such as tuberculosis, malaria and AIDS, it will be important to find better glycolipid adjuvants so we could improve new vaccine candidates for these public health problems (5,6).…”

Section: Introductionmentioning

confidence: 99%

Murine invariant natural killer T cells recognize glycolipids derived from extracts of the lichen Stereocaulon ramulosum

Baena

Gómez-Giraldo

Gómez

et al. 2015

Vitae

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Background: Invariant natural killer t cells (iNkt) can be activated by certain types of glycolipids that have the potential to generate adjuvant effects which could be used to develop effective and safe immunotherapies. Many of these glycolipids have been isolated from natural organisms, but there is a great amount of these organisms completely unexplored as a source of these types of compounds. Some of these organisms are lichens which are complex symbiotic organisms that have been showed to contain glycolipids. Objectives: We decide to test if glycolipids isolated from lichens would be able to activate iNkt cells in vitro and in vivo. Methods: We have used extracted glycolipids from 43 different species of lichens from Colombia. We have used iNkt hybridoma cells, C57BL/6 mice, IL-2 ELISA and the B16 melanoma to test for the adjuvant capabilities of glycolipids isolated from lichens. Results: In this study we have found two glycolipids with the capacity to activate iNkt cells in vitro. one of the glycolipids was able to activate iNkt cells in vivo, and was competent to induce protection against the B16 melanoma in the mouse model. Conclusions: We propose a possible chemical structure for a novel glycolipid called β-GalCer-lich (1) derived from the lichen Stereocaulon ramulosum.

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Optimizing NKT Cell Ligands as Vaccine Adjuvants

Cited by 76 publications

References 112 publications

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Mecanismos de activación de las células T asesinas naturales invariantes (iNKT)

Murine invariant natural killer T cells recognize glycolipids derived from extracts of the lichen Stereocaulon ramulosum

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