Differential expression of SAP and EAT‐2‐binding leukocyte cell‐surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4)

Abstract

The CD150 (SLAM) family consists of nine leukocyte cell-surface proteins involved in lymphocyte activation that belong to the immunoglobulin (Ig) superfamily. Six members of this family--CD84, CD150 (SLAM), CD229 (Ly9), CD244 (2B4), NTB-A, and CS1--associate with adapter proteins--SLAM-associated protein (SAP) and EAT-2. SAP is a short intracellular molecule that is mutated in humans with X-linked lymphoproliferative disease. Flow cytometric analysis of the expression of CD84, CD150, CD229, and CD244 cell-surface receptors on several leukocyte and lymphocyte subsets was performed. CD84 and CD150 were present on thymocytes, mature T cells and antigen-presenting cells. The expression of CD84 and CD150 was high on memory T cells. CD150 expression was strongly up-regulated after cell activation. In contrast to CD84, CD150 was absent on resting monocytes and immature dendritic cells (DCs). CD229 presented a pattern of expression restricted to lymphocytes. CD244 was preferentially expressed on natural killer cells, CD8(+) effector cells, resting monocytes, basophils, and eosinophils. We describe a broader distribution of CD84, CD150, CD229, and CD244 than previously reported and show that they are differentially expressed on hematopoietic cells. The heterogeneous expression of these receptors indicates that these molecules may play non-redundant functions in the regulation of both innate and adaptive immune responses.

Differential expression of CD150 (SLAM) family receptors by human hematopoietic stem and progenitor cells

“…These data indicate that in humans CD244 is a pan-hematopoietic progenitor/stem cell marker. This finding is surprising because until now this molecule was thought to be restricted to more mature or lineage-committed cell types such as human natural killer cells, a subset of cytotoxic T lymphocytes, basophils, and eosinophils [5,14]. Consistent with the expression pattern found in this study, it has been reported that only a small fraction of thymocytes express CD244, with positive cells corresponding to immature CD4 − CD8 − double-negative thymocytes [5].…”

“…These molecules, which act as cell-cell interaction and signaling receptors, are differentially expressed on distinct types of leukocytes and lymphocytes [5]. CD150 receptors are selectively expressed among primitive mouse progenitors in the adult BM in such a way that it is possible to highly purify HSCs using a simple combination of monoclonal antibodies (mAbs) against three of these receptors (CD150, CD244, and CD48) [6].…”

Properties of human blood monocytes ii. monocytes from healthy adults are highly heterogeneous within and among individuals

“…CD244 binds CD48 (63,64) and this interaction on NK and T cells can enhance cytolytic activity by those cells e.g., (65,66,67,68). It has been known for more than 10 years that CD244 also occurs on monocytes (21,22,23,24), but its function on monocytes has not been determined. The expression of these molecules on monocytes appears to be very closely regulated suggesting that they may have significant functions which could be elucidated by additional basic studies.…”

Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma

“…32 However, our findings indicate that CD229 is the SLAM family member with the highest potential for the development of myeloma-targeting therapies because: (i) CD229 showed the broadest expression of all SLAM members on myeloma cell lines and (ii) CD229 seems to have the most tumor-restricted expression of all SLAM members. 21,33 Accordingly, we have shown that CD229 is absent from monocytes and neutrophils. Most importantly CD34-positive cells, which represent the hematopoietic progenitor fraction, were also negative for CD229.…”