Anti-Human CD2 - Purified <i>in vivo</i> PLATINUM^TM Functional Grade - 1.0 mg

Human CD2 is a 351 amino acid transmembrane glycoprotein that is part of the immunoglobulin superfamily1, 2. CD2 is expressed on the surface of mature T cells, most NK cells, thymocytes, dendritic cells, and 9-12% of bone marrow cells. CD2 participates in T cell and NK cell activation and is important for thymocyte development and assembly of the immunological synapse1. However, the role of CD2 in murine immunity is not always consistent with its function in higher animals. CD2 is known to bind to lymphocyte-associated antigen 3 (CD58 and its murine analog CD48) as well as CD59.

LO-CD2a was developed as an immunosuppressive agent for use in organ allotransplantation3, 4. LO-CD2a was produced by immunizing a LOU/C rat with purified human T lymphocytes and fusing the splenocytes with the non-secreting rat fusion cell line IR983F, resulting in a rat IgG2b mAb of the IgK-1a allotype3.

LO-CD2a strongly inhibits mixed lymphocyte culture (MLC) 3 and induces T cell apoptosis5. Additionally, LO-CD2a does not induce proliferation of resting T cells3, and inhibits T cell proliferation induced by OKT3 antibody3, induces very low levels of cytokine release3, and also inhibits cytokine production induced by OKT33, LO-CD2a strongly inhibits proliferation of peripheral blood mononuclear cells stimulated with soluble OKT36, and induces human T cell hyporesponsiveness3. Adding LO-CD2a to a primary MLC inhibits the T cell proliferation response and has a subsequent inhibitory effect on the secondary immune response, thereby blocking primary and memory alloantigen proliferative responses. The human T cell hyporesponsiveness in the secondary MLC is restricted to alloantigens and occurs both in the absence of antibody and after cell surface re-expression of CD23.

The immune response is inhibited as a result of cell lysis by antibody-dependent cell mediated cytotoxicity (ADCC) induced by NK cells and activated monocytes and from CD2 down-modulation on CD2+ cells6. LO-CD2a has demonstrated immunosuppressive activity in vitro and effective T cell depletion in vivo. T cell unresponsiveness upon restimulation with the same antigen makes LO-CD2a distinct from other anti-CD2 antibodies7. The hyporesponsiveness induced by LO-CD2a has been used as a positive indicator of its potential efficacy on tolerance induction in allotransplantation3. Indeed, further studies have shown that humanized LO-CD2a (siplizumab) depletes the effector memory subset of T cells and promotes an expansion of alloreactive Tregs in vitro8. Additionally, in vivo experiments in chimpanzees infused with LO-CD2a or humanized siplizumab resulted in rapid depletion of CD2+ cells, with siplizumab having a favorable safety profile9.

CD2 is expressed on all mature human T cells, most thymocytes, NK cells and a small proportion of bone marrow cells.

2-8°C