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.
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