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Molecular and Cellular Biology, August 2005, p. 6869-6878, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.6869-6878.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

HIP-55 Is Important for T-Cell Proliferation, Cytokine Production, and Immune Responses

Jin Han, Jr-Wen Shui, Xuejun Zhang, Biao Zheng, Shuhua Han, and Tse-Hua Tan^*

Department of Immunology, Baylor College of Medicine, Houston, Texas 77030

Received 20 January 2005/ Returned for modification 16 March 2005/ Accepted 16 May 2005

Engagement of the T-cell receptor (TCR) triggers a series of signaling events that lead to the activation of T cells. HIP-55 (SH3P7 or mAbp1), an actin-binding adaptor protein, interacts with and is tyrosine phosphorylated by ZAP-70, which is a crucial proximal protein tyrosine kinase for TCR signaling. HIP-55 is important for JNK and HPK1 activation induced by TCR signaling. In this study, we report the generation and characterization of HIP-55 knockout mice. We found that HIP-55 knockout mice were viable and fertile but showed decreased body weight and increased occurrence of death within the first 4 weeks after birth. The lymphoid organs in HIP-55 knockout mice showed cellularity and T-cell development comparable to that of the wild-type mice. HIP-55 knockout T cells displayed defective T-cell proliferation, decreased cytokine production, and decreased up-regulation of the activation markers induced by TCR stimulation. TCR internalization was slightly increased in HIP-55 knockout T cells. These phenotypes were accompanied by reduced immune responses, including antigen-specific antibody production and T-cell proliferation in HIP-55 knockout mice. The TCR-induced signaling events, including LAT/phospholipase C1 phosphorylation and HPK1/JNK activation, were partially defective in HIP-55 knockout T cells. These results demonstrate the importance of HIP-55 as an adaptor protein in the TCR signaling and immune system.

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* Corresponding author. Mailing address: Department of Immunology, Baylor College of Medicine, Houston, Texas 77030. Phone: (713) 798-4665. Fax: (713) 798-4665. E-mail: ttan{at}bcm.edu.

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Molecular and Cellular Biology, August 2005, p. 6869-6878, Vol. 25, No. 16
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.16.6869-6878.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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