Cell
Volume 76, Issue 4, 25 February 1994, Pages 651-663
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Article
Evidence for a differential avidity model of T cell selection in the thymus

https://doi.org/10.1016/0092-8674(94)90505-3Get rights and content

Abstract

Positive and negative selection of a lymphocytic choriomeningitis virus (LCMV) peptide-specific, H-2Db-restricted T cell clone (P14) was studied using TAP1 and TAP1+ mice transgenic for P14 T cell receptor (TCR) α and β genes. Positive selection of transgenic CD8+ P14 cells was impaired in TAP1 mice. Addition of the LCMV peptide to TAP1 fetal thymic organ cultures (FTOCs) at low and high concentrations induced positive and negative selection of CD8+ P14 cells, respectively, while addition of the same peptide to TAP1+ FTOCs induced negative selection even at low concentrations. Both types of selection were peptide specific. Thus, a critical parameter that controls the fate of a thymocyte seems to be the number of TCRs engaged with complexes of peptide and major histocompatibility complex. When this number is low, positive selection occurs, and when it is high, negative selection takes place. These findings support a differential avidity model of T cell selection.

References (46)

  • M. Attaya et al.

    Ham-2 corrects the class I antigen-processing defect in RMA-S cells

    Nature

    (1992)
  • M.J. Bevan

    In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells

    Nature

    (1977)
  • P.J. Bjorkman et al.

    The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens

    Nature

    (1987)
  • M.R. Cappechi

    Altering the genome by homologous recombination

    Science

    (1989)
  • K. Falk et al.

    Allele-specific motifs revealed by sequencing of self-peptides from MHC molecules

    Nature

    (1991)
  • P.J. Fink et al.

    H-2 antigens of the thymus determine lymphocyte specificity

    J. Exp. Med.

    (1978)
  • D.H. Fremont et al.

    Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb

    Science

    (1992)
  • K.A. Hogquist et al.

    Positive selection of CD8+ T cells induced by major histocompatibility complex binding peptides in fetal thymus organ culture

    J. Exp. Med.

    (1993)
  • P. Hugo et al.

    Positive selection of TCR αβ thymocytes: is cortical thymic epithelium an obligatory participant in the presentation of major histocompatability complex protein?

    Immunol. Rev.

    (1993)
  • H. Jacobs et al.

    Mutations in the MHC class I antigen presenting groove affect both negative and positive selection of T cells

    Eur. J. Immunol.

    (1990)
  • P. Kisielow et al.

    Positive selection of antigen specific T cells in the thymus by restricting MHC molecules

    Nature

    (1988)
  • N.A. Lee et al.

    CD8 surface expression alter the fate of αβ T cell receptor-expressing thymocytes in transgenic mice

    J. Exp. Med.

    (1992)
  • H.-G. Ljunggren et al.

    Host resistance directed selectively against H-2 deficient lymphoma variants: analysis of the mechanism

    J. Exp. Med.

    (1985)
  • Cited by (0)

    Present address: Vanderbilt Medical School, Department of Microbiology and Immunology, Nashville, Tennessee 37232.

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