Induction of peptide-specific CD8+ CTL clones in β2-microglobulin- deficient mice

J. R. Cook, J. C. Solheim, J. M. Connolly, T. H. Hansen

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

We have examined the ability of β2-m- mice to produce CD4-8+ T cells by generating CD8+ CTLs to a defined ligand. We report here the first demonstration of peptide-specific, self-class I MHC-restricted CTLs from β2-m-deficient mice. We have used the KOD mouse, an H-2(d) β2-m- strain, to generate CTLs that recognize the class I MHC molecule L(d) in association with one of two L(d)-binding immunogenic peptides. Testing of these CTLs on a panel of L(d)-binding peptides reveals a high degree of peptide specificity. Peptide-specific CTL bulk cultures from KOD mice differ from those generated in β2-m+ mice in that they possess altered affinities for their peptide ligands. In addition, we show that CTLs generated from β2-m- mice in the presence of β2-m+ stimulator cells and exogenous peptide are specific either for the exogenous peptide or for endogenous peptides that are present in association with L(d) on the surface of β2-m+ cells, but are not present at detectable levels on β2-m- cells. These results demonstrate that positive selection of CD8+ CTLs can occur in vivo on the very low levels of class I MHC found in the KOD mouse. Furthermore, CTLs from the KOD mouse maintain a high degree of peptide specificity despite reduced levels of class I MHC.

Original languageEnglish (US)
Pages (from-to)47-57
Number of pages11
JournalJournal of Immunology
Volume154
Issue number1
StatePublished - 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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