Affiliation:
1. From the Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; and the Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892
Abstract
Recent data indicate that the cell surface glycoprotein CD5 functions as a negative regulator of T cell receptor (TCR)-mediated signaling. In this study, we examined the regulation of CD5 surface expression during normal thymocyte ontogeny and in mice with developmental and/or signal transduction defects. The results demonstrate that low level expression of CD5 on CD4−CD8− (double negative, DN) thymocytes is independent of TCR gene rearrangement; however, induction of CD5 surface expression on DN thymocytes requires engagement of the pre-TCR and is dependent upon the activity of p56lck. At the CD4+CD8+ (double positive, DP) stage, intermediate CD5 levels are maintained by low affinity TCR–major histocompatibility complex (MHC) interactions, and CD5 surface expression is proportional to both the surface level and signaling capacity of the TCR. High-level expression of CD5 on DP and CD4+ or CD8+ (single positive, SP) thymocytes is induced by engagement of the α/β-TCR by (positively or negatively) selecting ligands. Significantly, CD5 surface expression on mature SP thymocytes and T cells was found to directly parallel the avidity or signaling intensity of the positively selecting TCR–MHC-ligand interaction. Taken together, these observations suggest that the developmental regulation of CD5 in response to TCR signaling and TCR avidity represents a mechanism for fine tuning of the TCR signaling response.
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Reference52 articles.
1. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens: two parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views;Ledbetter;J Exp Med,1980
2. The “Ly-1 B” cell subpopulation in normal, immunodefective, and autoimmune mice;Hayakawa;J Exp Med,1983
3. Early T lymphocytes: differentiation in vivo of adult intrathymic precursor cells;Fowlkes;J Exp Med,1985
4. Molecular cloning of Ly-1, a membrane glycoprotein of mouse T lymphocytes and a subset of B cells: molecular homology to its human counterpart Leu-1/T1 (CD5);Huang;Proc Natl Acad Sci USA,1987
5. The B-cell surface protein CD72/Lyb2 is the ligand for CD5;Van De Helde;Nature,1991
Cited by
578 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献