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

Caria J. Aldrich, Robert E Hammer, Sharon Jones-Youngblood, Ulrich Koszinowski, Lee Hood, Iwona T Stroynowski, James Morse Forman D.M.D/Ph.D.

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

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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

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

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

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.",
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AU - Aldrich, Caria J.

AU - Hammer, Robert E

AU - Jones-Youngblood, Sharon

AU - Koszinowski, Ulrich

AU - Hood, Lee

AU - Stroynowski, Iwona T

AU - Forman D.M.D/Ph.D., James Morse

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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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