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Genetic Analysis of Responsiveness to Adjuvant-Free Immunological Signals: Transfer of Genes from Responder Strains (SJL/J And CE/J) to a Nonresponder Background Uncovers a Requirement for H-2 Heterozygosity

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Protein Conformation as an Immunological Signal

Abstract

In general, soluble protein antigens administered as deaggregated adjuvant-free solutions serve as poor immunologic signals1–3. Although this unresponsiveness to soluble proteins has been under investigation over the years, only recent studies with inbred mice (using bacterial β-D-galactosidase as the antigen) have demonstrated that it is under genetic control4. It was observed that while the majority (94%) of the inbred strains tested were unresponsive, SJL/J and CE/J mice produced high levels of specific IgG. This immune response (Ir)1 was shown to depend on two genetic loci, Ir-Z1 and ir-Z2, each segregating (in F2 and backcrosses) as a single, autosomal gene: Ir-Z1 of SJL/J as dominant and ir-Z2 of CE/J as recessive. Since there is no discernible association between H-2 haplotype (of independent origin) and responsiveness4, we concluded at that time that the chromosomal location of Ir-Z genes differs from that of well known Ir genes which are either closely linked to the H-2 region or to immunoglobulin structural genes. Based on these premises, we intorduced Ir-z genes into the nonresponder background of C57BL/6J by using conventional backcrossing5 in conjunction with selective breeding of responders. Our expectation was that this procedure would yield congenic inbred lines differing in responsiveness to adjuvant-free β-D-galactosidase.

Supported by United State Public Health grant CA-24440 from the National Cancer Institute.

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Abbreviations

Ir:

immune responses

Z:

β-D-galactosidase from Escherichia coli

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© 1983 Plenum Press, New York

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Rotman, B., Depasquale, M.J. (1983). Genetic Analysis of Responsiveness to Adjuvant-Free Immunological Signals: Transfer of Genes from Responder Strains (SJL/J And CE/J) to a Nonresponder Background Uncovers a Requirement for H-2 Heterozygosity. In: Celada, F., Schumaker, V.N., Sercarz, E.E. (eds) Protein Conformation as an Immunological Signal. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3778-2_37

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  • DOI: https://doi.org/10.1007/978-1-4613-3778-2_37

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3780-5

  • Online ISBN: 978-1-4613-3778-2

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