Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules

Carla Aldrich, Robert E. Hammer, Sharon Jones-Youngblood, Ulrich Koszinowski, Lee Hood, Iwona Stroynowski, James Forman

Research output: Contribution to journalArticle

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Abstract

THE α1-and α2-domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire1-3. Although the α3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS (refs 4, 5). CD8 is important in the selection of T cells as anti-CD8 antibody injected into perinatal mice interfers with this process6. We previously used a hybrid class I molecule with the α1/α2 domains from Ld and the Q3 domain from Q7b and showed that this molecule binds an Ld-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes7. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-Ld cytotoxic T lymphocytes. In addition, positive selection of virus-specific Ld-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the α1/α2 domains of class I, the α3 domain plays an important part in both positive and negative selection of antigen-specific cells.

Original languageEnglish (US)
Pages (from-to)718-721
Number of pages4
JournalNature
Volume352
Issue number6337
StatePublished - Aug 22 1991
Externally publishedYes

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Cytotoxic T-Lymphocytes
Major Histocompatibility Complex
T-Lymphocytes
Antigens
Peptide T
Peptides
T-Cell Antigen Receptor
Transgenic Mice
Anti-Idiotypic Antibodies
Viruses

ASJC Scopus subject areas

  • General

Cite this

Aldrich, C., Hammer, R. E., Jones-Youngblood, S., Koszinowski, U., Hood, L., Stroynowski, I., & Forman, J. (1991). Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules. Nature, 352(6337), 718-721.

Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules. / Aldrich, Carla; Hammer, Robert E.; Jones-Youngblood, Sharon; Koszinowski, Ulrich; Hood, Lee; Stroynowski, Iwona; Forman, James.

In: Nature, Vol. 352, No. 6337, 22.08.1991, p. 718-721.

Research output: Contribution to journalArticle

Aldrich, C, Hammer, RE, Jones-Youngblood, S, Koszinowski, U, Hood, L, Stroynowski, I & Forman, J 1991, 'Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules', Nature, vol. 352, no. 6337, pp. 718-721.
Aldrich C, Hammer RE, Jones-Youngblood S, Koszinowski U, Hood L, Stroynowski I et al. Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules. Nature. 1991 Aug 22;352(6337):718-721.
Aldrich, Carla ; Hammer, Robert E. ; Jones-Youngblood, Sharon ; Koszinowski, Ulrich ; Hood, Lee ; Stroynowski, Iwona ; Forman, James. / Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules. In: Nature. 1991 ; Vol. 352, No. 6337. pp. 718-721.
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N2 - THE α1-and α2-domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire1-3. Although the α3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS (refs 4, 5). CD8 is important in the selection of T cells as anti-CD8 antibody injected into perinatal mice interfers with this process6. We previously used a hybrid class I molecule with the α1/α2 domains from Ld and the Q3 domain from Q7b and showed that this molecule binds an Ld-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes7. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-Ld cytotoxic T lymphocytes. In addition, positive selection of virus-specific Ld-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the α1/α2 domains of class I, the α3 domain plays an important part in both positive and negative selection of antigen-specific cells.

AB - THE α1-and α2-domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire1-3. Although the α3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS (refs 4, 5). CD8 is important in the selection of T cells as anti-CD8 antibody injected into perinatal mice interfers with this process6. We previously used a hybrid class I molecule with the α1/α2 domains from Ld and the Q3 domain from Q7b and showed that this molecule binds an Ld-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes7. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-Ld cytotoxic T lymphocytes. In addition, positive selection of virus-specific Ld-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the α1/α2 domains of class I, the α3 domain plays an important part in both positive and negative selection of antigen-specific cells.

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