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Endogenous retroviruses lead to the expression of a histocompatibility antigen detectable by skin graft rejection
Abstract:
Mov mouse strains differ from their respective, coisogenic partner strains by the embryonic, germ-line introduction of Moloney murine leukemia virus genomes. The possibility that retroviral insertions into the mouse genome resulted in gain or loss mutations at non-H-2 histocompatibility loci was investigated by reciprocal skin grafting between Mov mice and mice from coisogenic, background strains. Two B6-derived and eight 129-derived Mov strains were analyzed. B6 mice rejected skin from the viremic Mov-3 and Mov-14 strains, indicating that these mice had new histocompatibility antigens. No rejections were observed with reciprocal skin grafts exchanged between mice of the 129 background strain and 129-derived Mov strains, one of which (Mov-9) is viremic. To investigate the potential viral origin of the new histocompatibility antigen in Mov-14, lymphocytes from B6 mice primed in vivo with Mov-14 cells or skin were restimulated in vitro with Mov-14 spleen cells and with two retroviral-induced B6 lymphomas, MBL-2 and RBL-5. All three cell types stimulated cytotoxic lymphocytes that lysed Mov-14 Con A lymphoblasts, MBL-2 and RBL-5. The same cytotoxic lymphocytes lysed only lymphoblasts from the viremic Mov-9 strain when tested on cells from 129 and 129 Mov mice. Thus the insertion and expression of exogenous Moloney murine leukemia virus results in the appearance of a new histocompatibility antigen as defined by its stimulation of skin-graft rejection and cytotoxic effector T-cell generation. The non-H-2 histocompatibility antigen identified in this study has been designated H-43 and is encoded by genes mapping to different loci in different Mov strains. These observations suggest that at least a subgroup of non-H-2 histocompatibility antigens is encoded by endogenous retroviruses; the implications of these results for understanding the origin and the identity of non-H-2 histocompatibility antigens are discussed.
Insights
Moloney murine leukemia virus insertions in mice can create new histocompatibility antigens (H-43). These retroviral antigens trigger immune responses, including skin graft rejection and cytotoxic T-cell generation.
Area of Science:
- Immunology
- Genetics
- Virology
Background:
- Mov mouse strains possess Moloney murine leukemia virus genomes introduced via embryonic germ-line modification.
- Understanding non-H-2 histocompatibility loci mutations is crucial for immune response studies.
Purpose of the Study:
- Investigate if retroviral insertions in Mov mice cause mutations at non-H-2 histocompatibility loci.
- Determine if Moloney murine leukemia virus (MMLV) insertion leads to novel histocompatibility antigens.
Main Methods:
- Reciprocal skin grafting between Mov mice and coisogenic background strains.
- Analysis of two B6-derived and eight 129-derived Mov strains.
- In vitro lymphocyte restimulation and cytotoxic T-cell assays.
Main Results:
- B6 mice rejected skin from viremic Mov-3 and Mov-14 strains, indicating new histocompatibility antigens.
- No rejections occurred in reciprocal grafts between 129 background and 129-derived Mov strains.
- Cytotoxic lymphocytes stimulated by MMLV-infected cells lysed target cells expressing viral antigens, including those from Mov-9.
Conclusions:
- Exogenous Moloney murine leukemia virus insertion and expression generate new histocompatibility antigens (H-43).
- These antigens are defined by skin graft rejection and cytotoxic T-cell responses.
- A subset of non-H-2 histocompatibility antigens may originate from endogenous retroviruses.