Alpha/beta T-cell antigen receptor gene and protein expression occurs at early stages of thymocyte differentiation

Proc Natl Acad Sci U S A. 1988 Feb;85(4):1174-8. doi: 10.1073/pnas.85.4.1174.

Abstract

Alterations in gene expression that orchestrate eukaryotic cellular differentiation often require appropriate interactions between differentiating cells and a specialized microenvironment. During T-lymphocyte differentiation, immature thymocytes undergo a stringent intrathymic selection process that requires intimate contact with thymic stromal elements. Since this selection process generates T cells that are self-tolerant and recognize nominal antigen only within the context of self-major histocompatibility antigen complex molecules, it is possible that thymocyte/stromal cell interactions are mediated, in part, by antigen-specific receptors expressed on differentiating thymocytes. However, the developmental stage at which alpha/beta antigen-specific receptors are expressed during T-cell maturation has been a matter of debate. To address this issue, we have studied alpha/beta T-cell antigen receptor gene and protein expression on normal thymocyte subsets of AKR/J mice, as well as on a panel of AKR/J primary thymic lymphomas characterized for CD4 (L3T4) and CD8 (Lyt-2) differentiation antigen expression. The data unequivocally demonstrate that alpha/beta heterodimers are expressed not only on phenotypically mature thymocytes but also on the majority of CD4+8+ double-positive cells that comprise the predominant nonmature thymocyte subset. Furthermore, a fraction of thymocytes in the CD4-8- double-negative compartment, known to contain progenitor cells, also expresses readily detectable cell-surface alpha/beta receptors. Therefore, during the process of intrathymic selection, interactions between nonmature thymocytes and stromal cells via the antigen-receptor complex may play a pivotal role in T-cell differentiation and should be considered in formulating schemes for functional T-cell selection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Neoplasm / analysis
  • Cell Differentiation
  • Gene Expression Regulation
  • Lymphoma / immunology
  • Lymphoma / pathology
  • Mice
  • Mice, Inbred AKR / genetics
  • Mice, Inbred AKR / immunology
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology*
  • Thymus Gland / pathology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta