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

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

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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). CDS is important in the selection of T cells as anti-CDS 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 α3 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
DOIs
StatePublished - Jan 1 1991

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Aldrich, C. J., 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. https://doi.org/10.1038/352718a0