Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses

Ling Ni, Ingrid Gayet, Sandra Zurawski, Dorothee Duluc, Anne Laure Flamar, Xiao Hua Li, Amy O'Bar, Sandra Clayton, Anna Karolina Palucka, Gerard Zurawski, Jacques Banchereau, SangKon Oh

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Dectin-1, a C-type lectin recognizing fungal and mycobacterial pathogens, can deliver intracellular signals that activate dendritic cells (DCs), resulting in initiation of immune responses and expansion of Th17 CD4+ T cell responses. In this paper, we studied the roles of human Dectin-1 (hDectin-1) expressed on DCs in the induction and activation of Ag-specific CD8+ T cell responses. We first generated an agonistic anti-hDectin-1 mAb, which recognizes the hDectin-1 Glu143-Ile162 region. It bound to in vitro monocyte-derived DCs and to in vivo CD1c+CD1a+ dermal DCs but not to epidermal Langerhans cells. Anti-hDectin-1-mediated DC activation resulted in upregulation of costimulatory molecules and secretion of multiple cytokines and chemokines in a Syk-dependent manner. DCs activated with the anti-hDectin-1 mAb could significantly enhance both neo and foreign Ag-specific CD8+ T cell responses by promoting both the expansion of CD8+ T cells and their functional activities. We further demonstrated that delivering Ags to DCs via hDectin-1 using anti-hDectin-1-Ag conjugates resulted in potent Ag-specific CD8+ T cell responses. Thus, hDectin-1 expressed on DCs can contribute to the induction and activation of cellular immunity against intracellular pathogens, such as mycobacteria, that are recognized by DCs via Dectin-1. Vaccines based on delivering Ags to DCs with an agonistic anti-hDectin-1 mAb could elicit CD8+ T cell-mediated immunity. Copyright

Original languageEnglish (US)
Pages (from-to)3504-3513
Number of pages10
JournalJournal of Immunology
Volume185
Issue number6
DOIs
StatePublished - Sep 15 2010
Externally publishedYes

Fingerprint

CD8 Antigens
Dendritic Cells
T-Lymphocytes
Antigens
Langerhans Cells
Cellular Immunity
dectin 1
C-Type Lectins
Mycobacterium
Chemokines
Monocytes
Up-Regulation
Vaccines

ASJC Scopus subject areas

  • Immunology

Cite this

Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses. / Ni, Ling; Gayet, Ingrid; Zurawski, Sandra; Duluc, Dorothee; Flamar, Anne Laure; Li, Xiao Hua; O'Bar, Amy; Clayton, Sandra; Palucka, Anna Karolina; Zurawski, Gerard; Banchereau, Jacques; Oh, SangKon.

In: Journal of Immunology, Vol. 185, No. 6, 15.09.2010, p. 3504-3513.

Research output: Contribution to journalArticle

Ni, L, Gayet, I, Zurawski, S, Duluc, D, Flamar, AL, Li, XH, O'Bar, A, Clayton, S, Palucka, AK, Zurawski, G, Banchereau, J & Oh, S 2010, 'Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses', Journal of Immunology, vol. 185, no. 6, pp. 3504-3513. https://doi.org/10.4049/jimmunol.1000999
Ni, Ling ; Gayet, Ingrid ; Zurawski, Sandra ; Duluc, Dorothee ; Flamar, Anne Laure ; Li, Xiao Hua ; O'Bar, Amy ; Clayton, Sandra ; Palucka, Anna Karolina ; Zurawski, Gerard ; Banchereau, Jacques ; Oh, SangKon. / Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses. In: Journal of Immunology. 2010 ; Vol. 185, No. 6. pp. 3504-3513.
@article{2d0859237f734c59b41e3f856e966dd0,
title = "Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses",
abstract = "Dectin-1, a C-type lectin recognizing fungal and mycobacterial pathogens, can deliver intracellular signals that activate dendritic cells (DCs), resulting in initiation of immune responses and expansion of Th17 CD4+ T cell responses. In this paper, we studied the roles of human Dectin-1 (hDectin-1) expressed on DCs in the induction and activation of Ag-specific CD8+ T cell responses. We first generated an agonistic anti-hDectin-1 mAb, which recognizes the hDectin-1 Glu143-Ile162 region. It bound to in vitro monocyte-derived DCs and to in vivo CD1c+CD1a+ dermal DCs but not to epidermal Langerhans cells. Anti-hDectin-1-mediated DC activation resulted in upregulation of costimulatory molecules and secretion of multiple cytokines and chemokines in a Syk-dependent manner. DCs activated with the anti-hDectin-1 mAb could significantly enhance both neo and foreign Ag-specific CD8+ T cell responses by promoting both the expansion of CD8+ T cells and their functional activities. We further demonstrated that delivering Ags to DCs via hDectin-1 using anti-hDectin-1-Ag conjugates resulted in potent Ag-specific CD8+ T cell responses. Thus, hDectin-1 expressed on DCs can contribute to the induction and activation of cellular immunity against intracellular pathogens, such as mycobacteria, that are recognized by DCs via Dectin-1. Vaccines based on delivering Ags to DCs with an agonistic anti-hDectin-1 mAb could elicit CD8+ T cell-mediated immunity. Copyright",
author = "Ling Ni and Ingrid Gayet and Sandra Zurawski and Dorothee Duluc and Flamar, {Anne Laure} and Li, {Xiao Hua} and Amy O'Bar and Sandra Clayton and Palucka, {Anna Karolina} and Gerard Zurawski and Jacques Banchereau and SangKon Oh",
year = "2010",
month = "9",
day = "15",
doi = "10.4049/jimmunol.1000999",
language = "English (US)",
volume = "185",
pages = "3504--3513",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses

AU - Ni, Ling

AU - Gayet, Ingrid

AU - Zurawski, Sandra

AU - Duluc, Dorothee

AU - Flamar, Anne Laure

AU - Li, Xiao Hua

AU - O'Bar, Amy

AU - Clayton, Sandra

AU - Palucka, Anna Karolina

AU - Zurawski, Gerard

AU - Banchereau, Jacques

AU - Oh, SangKon

PY - 2010/9/15

Y1 - 2010/9/15

N2 - Dectin-1, a C-type lectin recognizing fungal and mycobacterial pathogens, can deliver intracellular signals that activate dendritic cells (DCs), resulting in initiation of immune responses and expansion of Th17 CD4+ T cell responses. In this paper, we studied the roles of human Dectin-1 (hDectin-1) expressed on DCs in the induction and activation of Ag-specific CD8+ T cell responses. We first generated an agonistic anti-hDectin-1 mAb, which recognizes the hDectin-1 Glu143-Ile162 region. It bound to in vitro monocyte-derived DCs and to in vivo CD1c+CD1a+ dermal DCs but not to epidermal Langerhans cells. Anti-hDectin-1-mediated DC activation resulted in upregulation of costimulatory molecules and secretion of multiple cytokines and chemokines in a Syk-dependent manner. DCs activated with the anti-hDectin-1 mAb could significantly enhance both neo and foreign Ag-specific CD8+ T cell responses by promoting both the expansion of CD8+ T cells and their functional activities. We further demonstrated that delivering Ags to DCs via hDectin-1 using anti-hDectin-1-Ag conjugates resulted in potent Ag-specific CD8+ T cell responses. Thus, hDectin-1 expressed on DCs can contribute to the induction and activation of cellular immunity against intracellular pathogens, such as mycobacteria, that are recognized by DCs via Dectin-1. Vaccines based on delivering Ags to DCs with an agonistic anti-hDectin-1 mAb could elicit CD8+ T cell-mediated immunity. Copyright

AB - Dectin-1, a C-type lectin recognizing fungal and mycobacterial pathogens, can deliver intracellular signals that activate dendritic cells (DCs), resulting in initiation of immune responses and expansion of Th17 CD4+ T cell responses. In this paper, we studied the roles of human Dectin-1 (hDectin-1) expressed on DCs in the induction and activation of Ag-specific CD8+ T cell responses. We first generated an agonistic anti-hDectin-1 mAb, which recognizes the hDectin-1 Glu143-Ile162 region. It bound to in vitro monocyte-derived DCs and to in vivo CD1c+CD1a+ dermal DCs but not to epidermal Langerhans cells. Anti-hDectin-1-mediated DC activation resulted in upregulation of costimulatory molecules and secretion of multiple cytokines and chemokines in a Syk-dependent manner. DCs activated with the anti-hDectin-1 mAb could significantly enhance both neo and foreign Ag-specific CD8+ T cell responses by promoting both the expansion of CD8+ T cells and their functional activities. We further demonstrated that delivering Ags to DCs via hDectin-1 using anti-hDectin-1-Ag conjugates resulted in potent Ag-specific CD8+ T cell responses. Thus, hDectin-1 expressed on DCs can contribute to the induction and activation of cellular immunity against intracellular pathogens, such as mycobacteria, that are recognized by DCs via Dectin-1. Vaccines based on delivering Ags to DCs with an agonistic anti-hDectin-1 mAb could elicit CD8+ T cell-mediated immunity. Copyright

UR - http://www.scopus.com/inward/record.url?scp=78649902080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649902080&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1000999

DO - 10.4049/jimmunol.1000999

M3 - Article

C2 - 20729328

AN - SCOPUS:78649902080

VL - 185

SP - 3504

EP - 3513

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -