A late-differentiation antigen associated with the helper inducer function of human T cells

Abstract

T lymphocytes possessing helper function produce soluble factors that greatly augment B-cell proliferation and differentiation into antibody-secreting cells. In humans the subset of T lymphocytes bearing the T4 surface antigen comprises most of the cells that display helper activity and recognize class II antigens of the major histocompatibility complex (MHC), while the subset bearing the T8 antigen comprises T cells recognizing class I MHC antigens and exhibiting cytotoxic or suppressor function. Monoclonal antibodies to T4 or T8 greatly inhibit the cognitive and effector function of cells with the corresponding phenotype. This function/phenotype correlation is not absolute, however, for there are many examples of T8-positive clones that recognize MHC class II antigens and have helper activity, as well as of T4-positive clones with suppressor or cytotoxic function. Recently a family of cell-surface neoantigens, which might be relevant to T-cell function and which are present on activated but not on resting T lymphocytes, has been identified in mouse and humans using monoclonal antibodies. Some of these antibodies block the cytolytic activity of alloreactive T-cell clones, suggesting the possible involvement of such molecules in the activation of cytotoxic T-cell clones or in the lytic process itself. We now describe a similar late-differentiation antigen (LDA1) that is expressed by human T lymphocytes only following activation and is recognized by a monoclonal antibody that inhibits the antibody-inducing helper function of T lymphocytes.

Cell surface antigen CD109 is a novel member of the α2 macroglobulin/C3, C4, C5 family of thioester-containing proteins

“…Indeed, in view of the putative complementlike spatially restricted thioester reactivity of activated CD109 and its location as a GPI-linked cell surface molecule, we suggest that CD109 may function as a membrane-bound cross-linking reagent, thereby mediating cell-substrate, cell-matrix, or cell-cell interactions that play roles in hematopoiesis, primary hemostasis, or innate immune responses. Consistent with this notion, the CD109 mAb LDA 1 has been reported to abrogate antibody-inducing T-cell helper function during a primary mixed-lymphocyte reaction, 7 suggesting that CD109 may play a role in T-cell-antigen-presenting cell or T-cell-B-cell interactions.…”

“…However, the observation that T-cell-dependent antibody production is abrogated in vitro by the CD109 mAb LDA 1 suggests that CD109 may play a role in B-cell-T-cell interactions. 7 As a first step toward elucidating the function of CD109, we have isolated and characterized a human CD109 cDNA. We report that CD109 is a novel member of the ␣2 macroglobulin (␣2M)/C3, C4, C5 family of thioester-containing proteins and demonstrate that native CD109 contains an intact thioester.…”

“…6 Antibodies to CD109 recognize monomeric polypeptides of about 170 kd and 150 kd in lysates of KG1a cells, T-cell lines, and activated T lymphoblasts, endothelial cells, and activated platelets. 3,[7][8][9][10][11] Peptide mapping and amino acid (aa) analysis indicate that the 150-kd form is likely derived proteolytically from the 170-kd form. 3,10 An additional band of about 120 kd that is occasionally observed arises through calcium-dependent proteolysis of the larger forms.…”

“…3,[7][8][9] After activation with a variety of agonists, platelets become CD109 ϩ , expressing approximately 2000 Ϯ 400 mAb 8A3 binding sites per cell. 3 The Gov platelet alloantigens, which have been implicated in posttransfusion purpura, neonatal alloimmune thrombocytopenia, and refractoriness to platelet transfusion, have recently been shown to correspond to noncarbohydrate platelet CD109 epitopes.…”

“…After T-cell activation in vitro, CD109 becomes detectable on CD4 ϩ and CD8 ϩ T cells by day 1, peaks by day 6, and thereafter decreases in the absence of additional interleukin-2. 3,[7][8][9] The precise function of CD109 on hematopoietic precursors and on activated platelets and T cells is unknown. However, the observation that T-cell-dependent antibody production is abrogated in vitro by the CD109 mAb LDA 1 suggests that CD109 may play a role in B-cell-T-cell interactions.…”