Mapping the dextran sulfate binding site on CD2

Abstract

Summary This study has analysed the binding of a series of anti-CD2 monoclonal anlibodies (MoAbs) to T cells in the presence of the suUated polysaccharide dextran sulfatc (2 3 sulfates/ monosaccharide, 500 kDa) (DXS) to define Ihe DXS binding site on CD2. The results show that DXS interacts primarily at theTl 11 epitope. Thus fiveanti-CD2 MoAbs which bound tothcTI 12 epitope were inhibited in their binding by DXS. In contrast, seven anti-CD2 MoAbs that totally inhibited sheep red blood cells (SRBC) rosetting (identifying the Til I epitope) were unaReeted in their binding to T cells in the presenee oI'DXS. Three MoAbs which partially inhibited SRBC rosetting and thereby definingonly part of theTl 1 [ epitope. were also inhibited in their binding by DXS. Consistent with the conelusion that (he DXS binding site on CD2 is associated with the Tl 12 epitope was the observation that interaetion of DXS with CD2 resulted in augmented binding of the four MoAbs defining theTl 13 epitope, possibly reflecting an increased expression of the TI li (activation. CD2R) epitope of CD2. Collectively, the data presented support the notion that a natural ligand for theTl 12 epitope of CD2 will be identified as a sulphated carbohydrate structure.

Anti-CD2 receptor and anti-CD2 ligand (CD48) antibodies synergize to prolong allograft survival.

“…The CTL (Table 1), proliferative (Table 2), and cytokine data ( Table 3) indicate that inhibition affects both precursor CTL and helper cells. It is not clear if the mechanism of tolerance induction is related to direct signaling effects of the mAbs themselves on T cells, to blocking of CD2-CD48 receptor-ligand interactions, or to inhibition of interactions of these molecules with other potential ligands (5)(6)(7). These are not mutually exclusive mechanisms and all may be important.…”

“…The combined use of antireceptor plus antiligand mAbs may be advantageous in blocking both T cells and APCs, and in blocking interactions with as yet unknown ligands. Recent findings have identified murine CD48 (4), and human CD59 (5,6), and sulfated carbohydrates (7) as potential ligands for CD2, in addition to the well-characterized human ligand CD58 (LFA-3). Murine CD48 (Blast-I, BCM1) has structural homology to human CD58, including glycosyl-phosphatidylinositol linkage to the cell membrane, and functions in signal transduction and activation of lymphoid cells (4,(8)(9)(10).…”

Mechanisms of inhibition of Cryptococcus neoformans by human lymphocytes

“…Hyaluronic acid is a mucopolysaccharide with alternating ␤-1-3 glucuronidic and ␤-1-4 glucosaminidic bonds. The anionic carbohydrate polymer dextran sulfate, which binds to multiple lymphocytic receptors, including the extracellular matrix protein receptor 4-1BB and the sheep erythrocyte receptor CD2 (5,34), was used to control for charge interactions. The growth of C. neoformans in wells containing putative ligands was similar to that in control wells (Fig.…”