TY - JOUR
T1 - Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein
AU - Hemmi, Hiroaki
AU - Zaidi, Neeha
AU - Wang, Bei
AU - Matos, Ines
AU - Fiorese, Christopher
AU - Lubkin, Ashira
AU - Zbytnuik, Lori
AU - Suda, Koji
AU - Zhang, Kenneth
AU - Noda, Masaki
AU - Kaisho, Tsuneyasu
AU - Steinman, Ralph M.
AU - Idoyaga, Juliana
PY - 2012/2/1
Y1 - 2012/2/1
N2 - Members of the triggering expressed on myeloid cells (Trem) receptor family fine-tune inflammatory responses. We previously identified one of these receptors, called Treml4, expressed mainly in the spleen, as well as at high levels by CD8α + dendritic cells and macrophages. Like other Trem family members, Treml4 has an Ig-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow up on our initial results that Treml4-Fc fusion proteins bind necrotic cells, we generated a knockout mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression did not impair uptake of dying cells by CD8α + dendritic cells or cross-presentation of cell-associated Ag to CD8 +T cells, suggesting overlapping function between Treml4 and other receptors in vivo. To further investigate Treml4 function, we took advantage of a newly generated mAb against Treml4 and engineered its H chain to express three different Ags (i.e., OVA, HIV GAGp24, and the extracellular domain of the breast cancer protein HER2). OVA directed to Treml4 was efficiently presented to CD8 + and CD4 + T cells in vivo. Anti-Treml4-GAGp24 mAbs, given along with a maturation stimulus, induced Th1 Ag-specific responses that were not observed in Treml4 knockout mice. Also, HER2 targeting using anti-Treml4 mAbs elicited combined CD4 + and CD8 + T cell immunity, and both T cells participated in resistance to a transplantable tumor. Therefore, Treml4 participates in Ag presentation in vivo, and targeting Ags with anti-Treml4 Abs enhances immunization of otherwise naive mice.
AB - Members of the triggering expressed on myeloid cells (Trem) receptor family fine-tune inflammatory responses. We previously identified one of these receptors, called Treml4, expressed mainly in the spleen, as well as at high levels by CD8α + dendritic cells and macrophages. Like other Trem family members, Treml4 has an Ig-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow up on our initial results that Treml4-Fc fusion proteins bind necrotic cells, we generated a knockout mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression did not impair uptake of dying cells by CD8α + dendritic cells or cross-presentation of cell-associated Ag to CD8 +T cells, suggesting overlapping function between Treml4 and other receptors in vivo. To further investigate Treml4 function, we took advantage of a newly generated mAb against Treml4 and engineered its H chain to express three different Ags (i.e., OVA, HIV GAGp24, and the extracellular domain of the breast cancer protein HER2). OVA directed to Treml4 was efficiently presented to CD8 + and CD4 + T cells in vivo. Anti-Treml4-GAGp24 mAbs, given along with a maturation stimulus, induced Th1 Ag-specific responses that were not observed in Treml4 knockout mice. Also, HER2 targeting using anti-Treml4 mAbs elicited combined CD4 + and CD8 + T cell immunity, and both T cells participated in resistance to a transplantable tumor. Therefore, Treml4 participates in Ag presentation in vivo, and targeting Ags with anti-Treml4 Abs enhances immunization of otherwise naive mice.
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U2 - 10.4049/jimmunol.1102541
DO - 10.4049/jimmunol.1102541
M3 - Article
C2 - 22210914
AN - SCOPUS:84863057056
SN - 0022-1767
VL - 188
SP - 1147
EP - 1155
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -