title: SH2D2A modulates T cell mediated protection to a B cell derived tumor in transgenic mice.
abstract: BACKGROUND
  T cell specific adapter protein (TSAd), encoded by the SH2D2A gene, modulates signaling downstream of the T cell receptor (TCR). Young, unchallenged SH2D2A-deficient C57BL/6 mice exhibit a relatively normal immune phenotype. To address whether SH2D2A regulates physiologic immune responses, SH2D2A-deficient TCR-transgenic BALB/c mice were generated. The transgenic TCR recognizes a myeloma-derived idiotypic (Id) peptide in the context of the major histocompatibility complex (MHC) class II molecule I-E(d), and confers T cell mediated resistance to transplanted multiple myeloma development in vivo.
  
  
  RESULTS
  The immune phenotype of SH2D2A-deficient C57BL/6 and BALB/c mice did not reveal major differences compared to the corresponding wild type mice. When challenged with myeloma cells, Id-specific TCR-transgenic BALB/c mice lacking SH2D2A displayed increased resistance towards tumor development. Tumor free TCR-transgenic SH2D2A-deficient mice had higher numbers of Id-specific single positive CD4+ thymocytes compared to TCR-transgenic wild-type mice.
  
  
  CONCLUSIONS
  Our results suggest a modulatory role for SH2D2A in T cell mediated immune surveillance of cancer. However, it remains to be established whether its effect is T-cell intrinsic. Further studies are required to determine whether targeting SH2D2A function in T cells may be a potential adjuvant in cancer immunotherapy.
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. tone.berge@medisin.uio.no
authors.forename: Tone
authors.initials: T
authors.lastname: Berge
authors.forename: Ingrid Helene Bø
authors.initials: IH
authors.lastname: Grønningsæter
authors.forename: Kristina Berg
authors.initials: KB
authors.lastname: Lorvik
authors.forename: Greger
authors.initials: G
authors.lastname: Abrahamsen
authors.forename: Stine
authors.initials: S
authors.lastname: Granum
authors.forename: Vibeke
authors.initials: V
authors.lastname: Sundvold-Gjerstad
authors.forename: Alexandre
authors.initials: A
authors.lastname: Corthay
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.forename: Anne
authors.initials: A
authors.lastname: Spurkland
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D011948:Receptors, Antigen, T-Cell; C402726:Sh2d2a protein, mouse