Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior |
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Authors: | Li Zhuqing Calzada Maria J Sipes John M Cashel Jo Anne Krutzsch Henry C Annis Douglas S Mosher Deane F Roberts David D |
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Institution: | Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1500, USA. |
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Abstract: | Thrombospondin (TSP)-1 has been reported to modulate T cell behavior both positively and negatively. We found that these opposing responses arise from interactions of TSP1 with two different T cell receptors. The integrin alpha4beta1 recognizes an LDVP sequence in the NH2-terminal domain of TSP1 and was required for stimulation of T cell adhesion, chemotaxis, and matrix metalloproteinase gene expression by TSP1. Recognition of TSP1 by T cells depended on the activation state of alpha4beta1 integrin, and TSP1 inhibited interaction of activated alpha4beta1 integrin on T cells with its counter receptor vascular cell adhesion molecule-1. The alpha4beta1 integrin recognition site is conserved in TSP2. A recombinant piece of TSP2 containing this sequence replicated the alpha4beta1 integrin-dependent activities of TSP1. The beta1 integrin recognition sites in TSP1, however, were neither necessary nor sufficient for inhibition of T cell proliferation and T cell antigen receptor signaling by TSP1. A second TSP1 receptor, CD47, was not required for some stimulatory responses to TSP1 but played a significant role in its T cell antigen receptor antagonist and antiproliferative activities. Modulating the relative expression or function of these two TSP receptors could therefore alter the direction or magnitude of T cell responses to TSPs. |
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Keywords: | thrombospondins integrins chemotaxis T cell antigen receptor matrix metalloproteinases |
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