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Self-nonself discrimination by T cells.

H von Boehmer1, P Kisielow

  • 1Basel Institute for Immunology, Switzerland.

Science (New York, N.Y.)
|June 15, 1990
PubMed
Summary

The alpha beta T cell receptor (TCR) identifies foreign antigens presented by major histocompatibility complex (MHC) molecules. This interaction is crucial for T cell selection in the thymus, distinguishing self from non-self to prevent autoimmune responses.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The alpha beta T cell receptor (TCR) recognizes antigens bound to major histocompatibility complex (MHC) molecules.
  • T cell selection in the thymus differentiates self from non-self antigens to maintain immune tolerance.

Purpose of the Study:

  • To elucidate the mechanisms of T cell selection mediated by TCR-MHC interactions.
  • To understand how TCR binding to MHC molecules directs T cell differentiation.

Main Methods:

  • Analysis of TCR binding to self and foreign antigens presented by MHC molecules.
  • Investigation of T cell selection processes (positive and negative selection) in the thymus.
  • Examination of T cell differentiation into CD4+8- (helper) and CD4-8+ (killer) subsets.

Main Results:

  • TCRs binding to self-MHC plus self-antigen are deleted (negative selection).
  • TCRs binding to self-MHC in the absence of foreign antigen mature (positive selection).
  • TCR binding to MHC class I or class II molecules dictates differentiation into killer or helper T cells, respectively.

Conclusions:

  • TCR-MHC interactions are fundamental for T cell repertoire selection and immune homeostasis.
  • The thymus employs distinct selection processes to eliminate self-reactive T cells and mature functional T cells.
  • MHC class specificity of TCR binding is a key determinant of T cell effector function.

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