Molecular Cloning, Mapping to Human Chromosome 1 q21-q23, and Cell Binding Characteristics of Spα, a New Member of the Scavenger Receptor Cysteine-rich (SRCR) Family of Proteins

Abstract

CD5 and CD6, two type I cell surface antigens predominantly expressed by T cells and a subset of B cells, have been shown to function as accessory molecules capable of modulating T cell activation. Here we report the cloning of a cDNA encoding Sp␣, a secreted protein that is highly homologous to CD5 and CD6. Sp␣ has the same domain organization as the extracellular region of CD5 and CD6 and is composed of three SRCR (scavenger receptor cysteine rich) domains. Chromosomal mapping by fluorescence in situ hybridization and radiation hybrid panel analysis indicated that the gene encoding Sp␣ is located on the long arm of human chromosome 1 at q21-q23 within contig WC1.17. RNA transcripts encoding Sp␣ were found in human bone marrow, spleen, lymph node, thymus, and fetal liver but not in non-lymphoid tissues. Cell binding studies with an Sp␣ immunoglobulin (Sp␣-mIg) fusion protein indicated that Sp␣ is capable of binding to peripheral monocytes but not to T or B cells. Sp␣-mIg was also found to bind to the monocyte precursor cell lines K-562 and weakly to THP-1 but not to U937. Sp␣-mIg also bound to the B cell line Raji and weakly to the T cell line HUT-78. These findings indicate that Sp␣, a novel secreted protein produced in lymphoid tissues, may regulate monocyte activation, function, and/or survival.Leukocyte function is regulated by a discrete number of cell surface and secreted antigens that govern leukocyte activation, proliferation, survival, cell adhesion and migration, and effector function. Among the proteins that have been shown to regulate leukocyte function are members of the SRCR 1 family. This family of proteins can be divided into two groups based upon the number of cysteine residues per SRCR domain, intron-exon organization, and domain organization (1). Group B includes the cell surface proteins CD5 (2) and CD6 (3), which are predominantly expressed by thymocytes, mature T cells, and a subset of B cells, WC1 (4, 5), which is expressed by ␥␦ T cells in cattle, and M130 (6), which is expressed by activated monocytes. Of these, only CD5 and CD6 have been studied extensively. Monoclonal antibody (mAb) cross-linking studies suggest that both CD5 and CD6 can function as accessory molecules capable of modulating T cell activation (7,8). The role of CD5 and CD6 in the regulation of T cell function is further supported by the finding that following T cell activation, Tyr residues in the cytoplasmic domain of these two proteins are transiently phosphorylated. This provides a molecular mechanism whereby the cytoplasmic domains of both CD5 and CD6 can interact with intracellular SH2 containing proteins involved in signal transduction (9). Furthermore, phenotypic analysis of a CD5-deficient murine strain showed that its T cells are hyper-responsive to stimulation (10, 11), suggesting that CD5 expression is required for the normal regulation of T cell receptor (TCR)-mediated T cell activation.CD5 and CD6 are structurally the most closely related members of the group B SRCR family of proteins (1). They are both ty...

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