Heat-stable antigen/CD24 on mouse T lymphocytes: evidence for a costimulatory function.
Heat-stable antigen (HSA)/mouse CD24 (formerly termed Nectadrin) is a membrane glycoprotein with an unusual structure consisting of a small protein core and extensive glycosylation. It is expressed by hematopoietic cells but not by mature T lymphocytes. HSA on accessory cells is an important costimulatory molecule required for the clonal expansion of T lymphocytes. HSA is also involved in cell-cell adhesion events and the isolated antigen has been shown to possess self-binding properties. In the present study we have re-investigated the role of HSA in T cell proliferation. We find that following stimulation of T lymphocytes with concanavalin A or of CD4+ T lymphocytes with a combination of anti-CD3/CD28 monoclonal antibodies (mAb) the HSA antigen is transiently expressed. The expression correlated with the appearance of CD25 and a CD2 activation epitope at the cell surface. Induction of HSA was also seen in vivo on V beta 8+ T lymphocytes in BALB/c mice that were injected with Staphylococcal enterotoxin B. Biosynthetic labeling and analysis of mRNA by reverse transcriptase-polymerase chain reaction showed that HSA was synthesized by activated T lymphocytes. A combination of anti-CD3 and mAb 79 to HSA was incapable of inducing proliferation of purified CD4+ T lymphocytes. However, the antibody strongly enhanced the response obtained with a combination of anti-CD3/CD28 mAb. The augmenting effect of the HSA-specific mAb was dose dependent. Since HSA is bound to the membrane via a glycosyl-phosphatidylinositol (GPI) anchor and GPI-anchored molecules have been implicated in lymphocyte activation, it is conceivable that HSA is not only a costimulatory molecule on accessory cells but is also a signaling molecule in T lymphocytes. The possibility of a homotypic HSA/HSA interaction between T lymphocytes and accessory cells is discussed.
Hubbe
M
M
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
Altevogt
P
P
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D001483:Base Sequence; D051927:CD24 Antigen; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D017261:Glycosylphosphatidylinositols; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D017931:DNA Primers; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D012333:RNA, Messenger