Structurally Distinct T-cell Receptor Complexes on Developmentally Distinct T-cell Populations in Severe Combined Immunodeficiency Mice Expressing a Tcr-beta Transgene

EW Shores, T Nakayama, DL Wiest, Y Takahama, S Sharrow, A Singer

Research output: Contribution to journalArticlepeer-review

Abstract

T cell differentiation and TCR expression were assessed in severe combined immunodeficiency (SCID) mice possessing an already rearranged TCRV beta 8 transgene. Unlike nontransgenic SCID mice, TCRV beta 8-transgenic SCID mice contained a broad spectrum of T cell populations, including both immature thymocytes and mature T cells. In TCRV beta 8-transgenic SCID mice, immature CD4-CD8- and CD4+CD8+ thymocytes expressed surface TCR complexes structurally distinct from those expressed by mature single-positive T cells. Immature CD4+CD8+ thymocytes expressed surface TCR beta chains without a clonotypic TCR partner chain and largely without associated CD3 components. In contrast, mature single-positive T cells expressed fully assembled surface TCR complexes containing disulfide-linked heterodimers consisting of transgenic TCR beta chains and endogenous TCR alpha chains. The surface TCR complexes on mature T cells were associated with CD3 components and were competent to transduce TCR-mediated proliferative signals. Thus, T cells at different stages of development in TCRV beta 8-transgenic SCID mice express structurally distinct surface TCR complexes, demonstrating that the developmental stage achieved by T cells in these mice is related to the structure of the surface TCR complexes they express. Indeed, the present results indicate that successful differentiation into single-positive T cells requires surface expression of fully assembled TCR complexes.

Original languageAmerican English
Pages (from-to)1263-1275
Number of pages13
JournalJournal of Immunology
Volume150
Issue number4
StatePublished - Feb 15 1993

Keywords

  • Animals
  • CD4-Positive T-Lymphocytes/chemistry
  • CD8 Antigens/analysis
  • Cell Differentiation
  • Flow Cytometry
  • Mice
  • Mice, SCID/immunology
  • Mice, Transgenic
  • Phosphatidylinositols/chemistry
  • Receptors, Antigen, T-Cell, alpha-beta/chemistry
  • T-Lymphocyte Subsets/chemistry
  • Thymus Gland/cytology

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