Retroviruses and autoimmunity

Krieg, Arthur Μ.; Steinberg, Alfred D.

doi:10.1016/0896-8411(90)90137-h

Cited by 96 publications

(36 citation statements)

References 173 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies in human SLE patients have suggested that retroviral proteins may play a role in the production of autoantibodies (52-54; reviewed in Ref. 55). …”

Section: Discussionmentioning

confidence: 99%

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

Tucker¹,

Vyse

Rozzo

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

The F1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop an autoimmune disease that serves as a model for human systemic lupus erythematosus. Autoimmunity in (NZB × NZW)F1 mice includes the production of autoantibodies to the endogenous retroviral envelope glycoprotein, gp70, and gp70-anti-gp70 immune complexes (gp70 IC) have been implicated in the development of lupus nephritis in these animals. We used backcross and intercross combinations of C57BL/6 (B6; low gp70 levels) and NZB mice (high gp70 levels) to examine the contribution of serum gp70 Ag levels to the development of gp70 IC and nephritis. Analysis of (B6.H2z × NZB)F1 × NZB backcross mice and (NZB × B6)F2 mice showed a much stronger association of gp70 IC with kidney disease compared with IgG anti-chromatin autoantibodies in both populations of mice. Serum levels of gp70 correlated with production of gp70 IC in mice producing autoantibodies, although the overall effect on nephritis appeared to be small. Genetic mapping revealed three NZB-derived regions on chromosomes 2, 4, and 13 that were strongly linked with increased gp70 levels, and together, accounted for over 80% of the variance for this trait. However, additional linkage analyses of these crosses showed that loci controlling autoantibody production rather than gp70 levels were most important in the development of nephritogenic immune complexes. Together, these studies characterize a set of lupus-susceptibility loci distinct from those that control autoantibody production and provide new insight into the components involved in the strong association of gp70 IC with murine lupus nephritis.

show abstract

“…Several studies in human SLE patients have suggested that retroviral proteins may play a role in the production of autoantibodies (52-54; reviewed in Ref. 55). …”

Section: Discussionmentioning

confidence: 99%

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

Tucker¹,

Vyse

Rozzo

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Immunization of disease-susceptible mice with a synthetic peptide corresponding to the major encephalitogenic site of mouse MBP (amino acids 1-11 of the native protein with the N-terminus modified by acetylation, referred to as Acl-11) has been shown to be sufficient to induce inflammatory CNS disease. Interestingly, examination of the reactivity of T cells arising as a result of this immunization reveals an initial response directed at Acl-1 1 , followed subsequently by strong responses to peptide epitopes corresponding to other portions of the MBP molecule (e.g., MBP 3547,[81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140]. This spreading of the T cell response to encompass other portions of the MBP molecule has been termed "intramolecular spreading" of the autoimmune repertoire.…”

Section: )mentioning

confidence: 99%

“…One exhaustively studied example of this is the response of lupus-prone mouse strains to the major mouse ERV envelope protein SU, or gp70. All mice express the ERV-encoded gp70 envelope protein, but the level of expression is higher in lupus-prone strains, probably because expression of the gp70 gene is induced in activated B cells, which are numerous in such mice (93). In (New Zealand black x New Zealand white)F, mice, which develop a severe accelerated form of murine lupus, high levels of anti-gp70 antibodies are present, and the antigen circulates in the form of immune complexes (94).…”

Section: Retroviruses and Autoimmunitymentioning

confidence: 99%

Mechanisms of autoimmune disease induction

Behar

Porcelli

1995

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…Usually, these viruses exist in silent forms in all cells. In some instances, however, mice naturally form an antibody against murine leukemia virus (MuLV), leading to autoimmune diseases like systemic lupus erythematosus (3). In such a situation, it is possible that the autoantigen of endogenous viral origin might play a role as a helper T-cell (Th) epitope.…”

mentioning

confidence: 99%

“…Peptide fr,20 was used as a negative control. The peptide corresponds to F-MuLV envi22-141 which binds I-Ab, but not I-Eh (3,13). Results are shown as the mean of triplicate experiments, with error bars showing SEM.…”

mentioning

confidence: 99%

Induction of Cross‐Reactivity in an Endogenous Viral Peptide Non‐Reactive to FBL‐3 Tumor‐Specific Helper T‐Cell Clones

Uenishi

Iwanami

Yamagishi

et al. 1998

Microbiology and Immunology

View full text Add to dashboard Cite

We previously reported a helper T-cell (Th) epitope (peptide i) which corresponded to the sequence ranging from positions 462 to 479 from the N-terminus of the Friend-murine leukemia virus (FMuLV) envelope protein (env462-479). Homologous sequences exist in both Moloney-murine leukemia (MMuLV env452-469) and endogenous AKV (AKV env4, 470) viruses, which differ from F-MuLV env462-479 in 5 and 7 amino acids, respectively. However, peptide i-specific Th clones did not respond to either of the corresponding exogenous or endogenous peptides. One amino acid substitution in M-MuLV env452 469 (Asn to Tyr at position 465: N465Y) and three amino acids in AKV env453 470 (H460S, A466Y and Y468H) endowed both peptides with the reactivity to one of the Th clones, F5-5, almost to the same degree as peptide i. However, the other Th clones responded differently to each of the modified endogenous peptides substituted by one to three amino acids. The cells responsive to the cross-reactive peptides occupied only a minor portion, if any, of the bulk cultured lymph node cells from peptide i-immune mice, and in particular, no significant response to the modified endogenous peptides was observed in repeated experiments. The exchange of at least 3 residues was necessary for the endogenous peptide to acquire sufficient cross-reactivity to two of the three Th clones. However, it was noticeable that a single substitution of alanine by tyrosine at the dominant T-cell receptor (TCR) contact position of the peptide it generated a weak but significant cross-reactivity to one of the three Th clones in this study. Thus, peptides of endogenous retroviral origin that would be modified by mutational events might become 'non-self' and prime Th cells leading to auto-antibody production and resulting in autoimmune disease.

show abstract

Retroviruses and autoimmunity

Cited by 96 publications

References 173 publications

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

Mechanisms of autoimmune disease induction

Induction of Cross‐Reactivity in an Endogenous Viral Peptide Non‐Reactive to FBL‐3 Tumor‐Specific Helper T‐Cell Clones

Contact Info

Product

Resources

About