The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3

Abstract

CD2 (known also as T11 (ref. 1), LFA-2 (ref. 2) and the erythrocyte rosette receptor (ref. 3] is a functionally important T lymphocyte surface glycoprotein of relative molecular mass 50,000 to 58,000 (Mr 50-58 K) which appears early in thymocyte ontogeny and is present on all mature T cells. Monoclonal antibodies to CD2 inhibit cytotoxic T-lymphocyte (CTL)-mediated killing by binding to the T lymphocyte and blocking adhesion to the target cell. Such antibodies also inhibit T helper cell responses including antigen-stimulated proliferation, interleukin-2 (IL-2) secretion, and IL-2 receptor expression. Certain combinations of monoclonal antibodies to CD2 epitopes trigger proliferation of peripheral blood T lymphocytes, cytotoxic effector function and expression of IL-2 receptors by thymocytes, resulting in thymocyte proliferation in the presence of exogenous IL-2 (ref. 11). These findings suggest that CD2 can function in signalling as well as being an adhesion molecule. To understand the role of CD2 in T-cell adhesion and activation, it is essential to define its natural ligand. Our previous observation that purified CD2 inhibits rosetting of T lymphocytes with sheep erythrocytes and can be absorbed by sheep erythrocytes suggested it also might bind with detectable affinity to human cells. We now report that CD2 binds to a cell-surface antigen known as lymphocyte function-associated antigen-3 (LFA-3) with high affinity, and can mediate adhesion of lymphoid cells via interaction with LFA-3.

Homophilic interaction of NTBA, a member of the CD2 molecular family: induction of cytotoxicity and cytokine release in human NK cells

“…According to this concept, the known ligands of the CD2-related proteins are represented by one or another member of this molecular family. In particular, it has been shown that these molecular interactions are either heterophilic, such as CD2/CD58, CD2/CD48, and CD244/ CD48, or homophilic, such as CD150/CD150, CD84/ CD84, and CS1/CS1 [22][23][24][25][26][27][28].…”

“…Both heterophilic and homophilic interactions have been described between different members of the CD2 family [22][23][24][25][26][27][28]. We therefore explored the possibility that NTBA may recognize one or another member of this family.…”

“…Different heterophilic or homophilic receptor/ligand interactions have been reported to occur between other members of the CD2 family. In particular, human CD2 binds CD58 [24], but it also binds with low affinity CD48 [25], whereas CD150 [26], CD84 [27], and CS1 [28] mediate homophilic interactions. In this study, using a soluble NTBA molecule we demonstrate that also NTBA recognizes itself.…”

The counterreceptor binding site of human CD2 exhibits an extended surface patch with multiple conformations fluctuating with millisecond to microsecond motions

“…CD2 mediates adhesion by binding to its counterreceptor CD58 in humans (Selvaraj et al, 1987). CD2-mediated adhesion facilitates T cell recognition of antigens by the T cell receptor (Moingeon et al, 1989b: Koyasu et al, 1990 J ( w N ) , and J(w"), spectral density function derived at zero, nitrogen, and proton frequencies, respectively; Jeg(0), in the absence of exchange its value equals J(0); Juvg(wH,).…”

Mapping the dextran sulfate binding site on CD2

“…T112 and T113 epitopes of CD2 and the consequent f cell activation process reflects an interaction of naturally occurring ligands involved in physiological T cell activation. Indeed there is compelling evidence that the LFA-3 molecule is a tigand fortheTIli epitope of CD2 both for T cell adhesion (6)(7)(8) and T cell activation (8)(9)(10). The identity of the ligands for the T112 and T113 epitopes remains to be established.…”