Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein

Hiroaki Hemmi, Neeha Zaidi, Bei Wang, Ines Matos, Christopher Fiorese, Ashira Lubkin, Lori Zbytnuik, Koji Suda, Kenneth Zhang, Masaki Noda, Tsuneyasu Kaisho, Ralph M. Steinman, Juliana Idoyaga

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1147-1155
Number of pages9
JournalJournal of Immunology
Volume188
Issue number3
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

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Antigen Presentation
Immunity
T-Lymphocytes
Knockout Mice
Dendritic Cells
Proteins
Cross-Priming
Myeloid Cells
Tail
Immunization
Spleen
Macrophages
HIV
Breast Neoplasms
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein. / Hemmi, Hiroaki; Zaidi, Neeha; Wang, Bei; Matos, Ines; Fiorese, Christopher; Lubkin, Ashira; Zbytnuik, Lori; Suda, Koji; Zhang, Kenneth; Noda, Masaki; Kaisho, Tsuneyasu; Steinman, Ralph M.; Idoyaga, Juliana.

In: Journal of Immunology, Vol. 188, No. 3, 01.02.2012, p. 1147-1155.

Research output: Contribution to journalArticle

Hemmi, H, Zaidi, N, Wang, B, Matos, I, Fiorese, C, Lubkin, A, Zbytnuik, L, Suda, K, Zhang, K, Noda, M, Kaisho, T, Steinman, RM & Idoyaga, J 2012, 'Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein', Journal of Immunology, vol. 188, no. 3, pp. 1147-1155. https://doi.org/10.4049/jimmunol.1102541
Hemmi, Hiroaki ; Zaidi, Neeha ; Wang, Bei ; Matos, Ines ; Fiorese, Christopher ; Lubkin, Ashira ; Zbytnuik, Lori ; Suda, Koji ; Zhang, Kenneth ; Noda, Masaki ; Kaisho, Tsuneyasu ; Steinman, Ralph M. ; Idoyaga, Juliana. / Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein. In: Journal of Immunology. 2012 ; Vol. 188, No. 3. pp. 1147-1155.
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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

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