Anti-HIV and Anti-Anti-MHC Antibodies in Alloimmune and Autoimmune Mice

Kion, Tracy A.; Hoffmann, Geoffrey W.

doi:10.1126/science.1909456

Cited by 135 publications

(49 citation statements)

References 19 publications

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“…A reagent that could permit the detection of such anti-center pole antibodies is gpl20. We found that anti-gpl20 antibodies can indeed be detected in hyperimmune alloantisera (44). Since the mice have never been immunized with gpl20, a reasonable interpretation is that the anti-gpl20 antibodies are anti-MHC-image antibodies.…”

Section: Aniti-hiv and Mhc-image Antibodies In Aflonimune Micementioning

confidence: 62%

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An idiotypic network model of AIDS immunopathogenesis.

Hoffmann

Kion

Grant

1991

Proc. Natl. Acad. Sci. U.S.A.

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Considerations from a network theory of the immune system suggest that human immunodeficiency virus and allogeneic stimuli may act synergistically to cause AIDS. The immune responses to these stimuli include two components that are directed against each other. In some AIDS risk groups other antigens that mimic major histocompatibility complex antigens may substitute for allogeneic stimuli. Implications for the prevention of AIDS are discussed.The idea that human immunodeficiency virus (HIV) is the sole cause of AIDS (without any cofactors) and is directly responsible for the depletion of CD4-bearing T cells is currently being questioned by many researchers for several reasons. A surprisingly low number of T cells are infected with HIV in AIDS (1), and immunosuppression occurs prior to depletion of CD4 cells (2). Furthermore, immunity against HIV does not protect against AIDS; AIDS patients have high quantities of anti-HIV antibodies in their sera (3) and generate a strong anti-HIV cytotoxic T-cell response (4) but are not protected. In fact, people tend to become seriously ill only after they make anti-HIV antibodies. In spite of intensive research, a detailed mechanism explaining T-cell depletion in vivo, only on the basis of HIV infection, has not been characterized.An alternative possibility being considered by several groups of researchers is that HIV induces a deleterious immune response that attacks the immune system itself (5-15). In this paper, we describe an immunological process that could lead to AIDS. Network RegulationThe recognition of variable (V) regions by lymphocytes and vice versa is widely believed to be a central aspect of the specific regulation of the immune system (16). The relative levels ofpopulations oflymphocytes and the topology oftheir interactions are then key aspects of a description of the system. Some lymphocyte populations recognize an invading antigen, and some have V regions that functionally resemble the antigen in that they have complementarity to the V regions of antigen-specific clones. Specific interactions between these populations are believed to regulate the immune response. An explicit network model accounts for a considerable range of phenomena, including memory, separate roles for IgM and IgG, helper T cells, suppressor T cells, and specific T-cell factors (10,11,(17)(18)(19)(20)(21).The theory we describe here emerges from that model. An important component of the theory is the concept of network focusing, which refers to the ability of the network to select clones that are images of particular antigens, including self antigens. A second component is the idea that there is a major axis of specificities in the immune system, bounded by self class I and class II major histocompatibility complex (MHC) antigens. We suggest AIDS is a consequence of a destabilization of the system after excessive stimulation along its major axis.T (Fig. 1). Each suppressor T cell is idiotypically connected to a large number of helper T cells and the suppressor T cells are said ...

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Section: Aniti-hiv and Mhc-image Antibodies In Aflonimune Micementioning

confidence: 62%

“…We also see anti-p24 antibodies in murine alloimmune sera (44). In view ofevidence of similarities between class II MHC and each of gpl20, gp4l, and Nef, it is possible that the anti-p24 activity is also due to crossreactivity between p24 and class II MHC image.…”

Section: Aniti-hiv and Mhc-image Antibodies In Aflonimune Micementioning

confidence: 68%

An idiotypic network model of AIDS immunopathogenesis.

Hoffmann

Kion

Grant

1991

Proc. Natl. Acad. Sci. U.S.A.

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“…Because the conserved domain of the envelope proteins of HIV-1 and HIV-2 are weakly immunogenic in native envelope configuration (36) Considering possible immune enhancement phenomena by antibodies against various epitopes of HIV envelope glycoproteins (38,39) and the superantigen and autoimmunity theories to explain the depletion of uninfected CD4-positive T lymphocytes (40,41), the chimeric gag virus-like particles provide an attractive option to develop a recombinant subunit vaccine using defined epitopes that can induce humoral and cell-mediated immunity against HIV infection.…”

Section: Discussionmentioning

confidence: 99%

Chimeric gag-V3 virus-like particles of human immunodeficiency virus induce virus-neutralizing antibodies.

Luo

Cannon

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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A 41-kDa unprocessed human immunodeficiency virus 2 (HIV-2) gag precursor protein that has a deletion of a portion of the viral protease assembles as virus-like particles by budding through the cytoplasmic membrane of recombinant baculovirus-infected insect cells. We have constructed six different combinations of chimeric genes by coupling the truncated HIV-2 gag gene to the neutralizing domain (V3) or the neutralizing and the CD4 binding dons

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“…Sequence similarities have been reported between major histocompatibility complex (MHC) class II, particularly HLA-DR and HLA-DQ, and gpl20 (18,19), HIV-1 Nef (20) and gp4l (21), and between the major retroviral capsid protein (CA) and regions in the Sm-BB' autoantigen, the SSB/La antigen, the 70-kDa ribonucleoprotein, topoisomerase I, and acetylcholine receptor (22,23). Finally, Hoffman and colleagues (24,25) struction of IgG1 K/A Fab libraries using the pComb3 M13 surface display system have been described (27,28,32).…”

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confidence: 99%