The receptor function of CD2 in human CD2 transgenic mice is based on highly conserved associations with signal transduction molecules.
The activation of human T cells via CD2 in response to mitogenic monoclonal antibodies (mAbs) typically requires that one mAb is specific for an epitope within the N-terminal Ig domain of CD2 and the other for a partially hidden epitope. We have examined the proliferative response of human T cells and human CD2 (huCD2) transgenic murine T cells to two novel CD2 monoclonal antibodies, AICD2.M1 and AICD2.M2, and have partially mapped the epitopes of these and other mitogenic CD2-specific monoclonal antibodies by way of recognition of CD2:CD58 chimeric proteins possessing either the N-terminal or the membrane proximal immunoglobulin domains of CD2. To understand the molecular basis of proliferation in huCD2 transgenic murine T cells, the interactions of huCD2 with signaling proteins in murine T cells were analyzed. The transgenic huCD2 molecule was found to interact with the murine tyrosine kinases p56lck and p59fyn and the CD3-epsilon and zeta chains of the TCR/CD3 signaling complex and to coimmunoprecipitate tyrosine phosphatase activity. These molecular associations resemble the situation in human T cells and suggest that human CD2 couples to the same signal transduction pathways in humans and transgenic mice.
Wild
M K
MK
Institute for Immunology, Ruprecht-Karls-Universität, Heidelberg, Germany.
Verhagen
A M
AM
Meuer
S C
SC
Schraven
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018801:CD2 Antigens / Q000502:physiology*; D018604:Epitope Mapping; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D011971:Receptors, Immunologic; D017493:Leukocyte Common Antigens