Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses

Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10495-500. doi: 10.1073/pnas.0802423105. Epub 2008 Jul 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / chemistry*
  • Antigens, CD / metabolism
  • B7 Antigens
  • B7-1 Antigen / chemistry
  • B7-1 Antigen / metabolism
  • CD3 Complex / biosynthesis
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Dermatitis, Contact
  • Gene Expression Regulation
  • Humans
  • Immune System
  • Interferon-gamma / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Rats
  • Receptors, Immunologic / biosynthesis*
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / metabolism
  • Receptors, Immunologic / physiology

Substances

  • Antigens, CD
  • B7 Antigens
  • B7-1 Antigen
  • CD276 protein, human
  • CD3 Complex
  • Cd276 protein, mouse
  • Receptors, Immunologic
  • TLT-2 protein, mouse
  • TREML2 protein, human
  • Interferon-gamma