Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses.
The B7 family member B7-H3 (CD276) plays important roles in immune responses. However, the function of B7-H3 remains controversial. We found that murine B7-H3 specifically bound to Triggering receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2, TREML2). TLT-2 was expressed on CD8(+) T cells constitutively and on activated CD4(+) T cells. Stimulation with B7-H3 transfectants preferentially up-regulated the proliferation and IFN-gamma production of CD8(+) T cells. Transduction of TLT-2 into T cells resulted in enhanced IL-2 and IFN-gamma production via interactions with B7-H3. Blockade of the B7-H3:TLT-2 pathway with a mAb against B7-H3 or TLT-2 efficiently inhibited contact hypersensitivity responses. Our results demonstrate a direct interaction between B7-H3 and TLT-2 that preferentially enhances CD8(+) T cell activation.
Hashiguchi
Masaaki
M
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Kobori
Hiroko
H
Ritprajak
Patcharee
P
Kamimura
Yosuke
Y
Kozono
Haruo
H
Azuma
Miyuki
M
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000737:chemistry / Q000378:metabolism; D017252:CD3 Complex / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003877:Dermatitis, Contact; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology
D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; C423237:CD276 protein, human; D017252:CD3 Complex; C486038:Cd276 protein, mouse; D011971:Receptors, Immunologic; C530953:TLT-2 protein, mouse; C473367:TREML2 protein, human; D007371:Interferon-gamma