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Mouse model for analysis of non-MHC genes that influence allogeneic response: recombinant congenic strains of OcB/Dem series that carry identical H2 locus

  • Research Article
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Central European Journal of Biology

Abstract

Alloreactivity is the strongest known primary immune response. Its clinical manifestations are graft rejection, graft-versus-host disease and graft-versus-leukemia effect. The strongest stimulation by allogeneic cells is due to incompatibility at the major histocompatibility complex (MHC) genes. However, the non-MHC genes also participate in allogeneic response. Here we present a mouse model for study of the role of non-MHC genes in regulation of alloreactivity and show that they besides encoding antigens also regulate the responsiveness. Recombinant congenic strains (RCS) of O20/A (O20)-c-B10.O20/Dem (OcB/Dem) series have been derived from the parental strains O20 and B10.O20, which carry identical MHC haplotypes (H2pz) and therefore their differences in alloantigen response depend only on non-MHC genes. We have tested a MLR response by spleen cells of the strains O20, B10.O20, and 16 OcB/Dem strains through stimulation by cells from strains C57BL/10 (H2b), BALB/c (H2d), CBA (H2k), and DBA/1 (H2q) alloantigens. Proliferative response of O20, B10.O20 and OcB/Dem strains to these four alloantigens exhibited a similar but not completely identical pattern of reactivity. The responses to different alloantigens were highly correlated: C57BL/10-BALB/c r = 0.87, C57BL/10-CBA r = 0.84, C57BL/10-DBA/1 r = 0.83. Cluster analysis of the responses by O20, B10.O20, and OcB mice identified groups of strains with distinct patterns of response. This data shows that two main types of genes influence MLR: 1. structural genes for major and minor alloantigens and 2. genes regulating T-cell receptor signal transduction or mediating costimulatory signals by antigen-presenting cells.

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Abbreviations

GVHD:

graft-versus-host-disease

IL:

interleukin

MHC:

major histocompatibility complex

MLR:

mixed lymphocyte response

MLC:

mixed lymphocyte culture

RCS:

recombinant congenic strains

TGF:

transforming growth factor

TNF:

tumor necrosis factor

QTL:

quantitative trait loci

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Authors and Affiliations

  1. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 166 37, Prague, Czech Republic

    Helena Havelková, Vladimír Holáň, Igor Kárník & Marie Lipoldová

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  1. Helena Havelková
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  2. Vladimír Holáň
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  3. Igor Kárník
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  4. Marie Lipoldová
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Havelková, H., Holáň, V., Kárník, I. et al. Mouse model for analysis of non-MHC genes that influence allogeneic response: recombinant congenic strains of OcB/Dem series that carry identical H2 locus. cent.eur.j.biol. 1, 16–28 (2006). https://doi.org/10.2478/s11535-006-0002-x

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  • DOI: https://doi.org/10.2478/s11535-006-0002-x

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