Cytotoxic T lymphocytes from mice with soluble class I Q10 molecules in their serum are not tolerant to membrane-bound Q10

D. W. Mann, I. Stroynowski, L. Hood, J. Forman

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Q10 is a class I Qa-2 region-encoded mocecule that is secreted by the liver and present in serum at high concentrations (about 10 to 60 μg/ml) in most strains of mice. The amino terminal portion of this molecule can also be expressed as an integral membrane protein by splicing the 5' end of the Q10 gene to the 3' end of H-2L(d) and transfecting the hybrid gene into murine L cells. Because CTL primarily recognize polymorphic determinants controlled by the α1 and α2 domains of class I molecules and because the Q10(d)/L(d) product expressed by transfected L cells includes the α1 and the α2 domains of Q10(d), we could address whether mice bearing serum Q10 were tolerant to this molecule at the CTL level. The results of these experiments demonstrate that Q10+ mice are able to generate H-2-unrestricted CTL activity against Q10(d) expressed on transfected L cells, and this response was not inhibitable by the addition of Q10-containing normal mouse serum. It is unlikely that this CTL activity is due to possible polymorphic differences in Q10 alleles, since semi-syngeneic BALB/c (H-2(d)) mice, from which the Q10(d) hybrid gene construct was derived, are able to generate anti-Q10(d) effector cells. The Q10(d) molecule was shown to cross-react with H-2L(d), lending support to the concept that Qa genes can serve as donors for polymorphic sequences found in H-2K, -D, and -L. That mice can generate anti-Q10 CTL activity suggests that this soluble class I protein does not act as a toleragen for these cells. The implications of these findings for an understanding of self-tolerance are discussed.

Original languageEnglish (US)
Pages (from-to)240-245
Number of pages6
JournalJournal of Immunology
Volume138
Issue number1
StatePublished - Jan 1 1987

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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