Sh2d2a, which encodes the T-cell specific adapter protein (TSAd), is involved in modulating signaling downstream of the T-cell receptor (TCR) [1,3,4,5]. Its expression in T-cells is regulated at both transcriptional and translational levels, and cAMP signaling along with TCR engagement play key roles in this regulation [3]. The gene may be important for proper T-cell activation and has potential implications in immune-related biological processes [3]. Genetic models, such as knockout mouse models, can be valuable for studying its functions.

In TCR-transgenic BALB/c mice lacking Sh2d2a, there was increased resistance towards the development of transplanted multiple myeloma. These tumor-free knockout mice also had higher numbers of Id-specific single positive CD4+ thymocytes, suggesting a modulatory role for Sh2d2a in T-cell mediated immune surveillance of cancer [1]. Additionally, a loss-of-function frameshift mutation of Sh2d2a in tumor-infiltrating lymphocytes could activate T-cell effector functions in vitro, indicating its potential impact on antitumor immunity [2].

In conclusion, Sh2d2a is crucial for regulating T-cell activation and has a significant role in T-cell mediated immune surveillance of cancer. The use of Sh2d2a knockout mouse models has provided valuable insights into its functions in cancer-related immune responses, suggesting it could be a potential target for cancer immunotherapy [1].

References:

1. Berge, Tone, Grønningsæter, Ingrid Helene Bø, Lorvik, Kristina Berg, Bogen, Bjarne, Spurkland, Anne. 2012. SH2D2A modulates T cell mediated protection to a B cell derived tumor in transgenic mice. In PloS one, 7, e48239. doi:10.1371/journal.pone.0048239. https://pubmed.ncbi.nlm.nih.gov/23144743/

2. Mukohara, Fumiaki, Iwata, Kazuma, Ishino, Takamasa, Kawazu, Masahito, Togashi, Yosuke. 2024. Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2320189121. doi:10.1073/pnas.2320189121. https://pubmed.ncbi.nlm.nih.gov/39167601/

3. Kolltveit, Kristin Melkevik, Granum, Stine, Aasheim, Hans-Christian, Schenck, Karl, Spurkland, Anne. 2007. Expression of SH2D2A in T-cells is regulated both at the transcriptional and translational level. In Molecular immunology, 45, 2380-90. doi:. https://pubmed.ncbi.nlm.nih.gov/18160104/

4. Dai, K Z, Harbo, H F, Celius, E G, Vartdal, F, Spurkland, A. . The T cell regulator gene SH2D2A contributes to the genetic susceptibility of multiple sclerosis. In Genes and immunity, 2, 263-8. doi:. https://pubmed.ncbi.nlm.nih.gov/11528519/

5. Granum, Stine, Sundvold-Gjerstad, Vibeke, Dai, Ke-Zheng, Lea, Tor, Spurkland, Anne. 2006. Structure function analysis of SH2D2A isoforms expressed in T cells reveals a crucial role for the proline rich region encoded by SH2D2A exon 7. In BMC immunology, 7, 15. doi:. https://pubmed.ncbi.nlm.nih.gov/16839418/