Cells that express viral antigens but lack H-2 determinants are not lysed by immune thymus-derived lymphocytes but are lysed by other antiviral immune attack mechanisms.

Zinkernagel, Rolf M.; Oldstone, Michael B. A.

doi:10.1073/pnas.73.10.3666

Cited by 63 publications

(28 citation statements)

References 43 publications

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“…Repeated experiments, however, revealed that this cell line was immune to killing by sensitized T lymphocytes. Taking into account the recent hypothesis (Zinkernagel and Oldstone 1976) that H-2 antigen expression is necessary for cytolysis at the post-recognition stage and that K-and D-coded major transplantation antigens may have the special function of serving as structures by which the T cell punctures the target cell wall, we investigated the possibility that altered H-2 antigen expression might explain the lack of response of BL/VL 3 cells in alloreactive CML assays. …”

Section: Introductionmentioning

confidence: 99%

H-2 antigen expression: Loss in vitro, restoration in vivo, and correlation with cell-mediated cytotoxicity in a mouse lymphoma cell line

1978

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The susceptibility to cell-mediated cytolysis of cells of the recently developed C57BL/Ka(H-2 ( b )) lymphoma cell line, BL/VL(3), was investigated in allogeneic assays with thymus-dependent lymphocytes (T cells). Compared to EL4, the widely used C57BL/6(H-2 ( b )) lymphoma cell line, BL/VL(3) cells were found to be insensitive to T-cell-mediated lysis as detected by the use of(51)Crrelease methods. When used as immunogens in alloreactive combinations with BALB/c(H-2 ( d )) splenocytes as responder cells, BL/VL(3) cells failed to elicit sensitization. Serological tests showed that this cell line had profoundly reduced levels of H-2(b) antigens on its surface. When BL/VL(3) cells were reinjected into C57BL/Ka and BALB/c mice, full recovery of H-2(b) antigen expression at the cell surface was observed in both syngeneic and allogeneic hosts after only 11 days of in vivo growth. Concomitantly, they acquired the ability to induce cytotoxic responses in allogeneic T cells and became susceptible to their lytic activity. The expression of H-2 antigens on the surface of BL/VL(3) cells is a reversibly modulated function that depends on in vivo growth conditions and is lost in vitro in the absence of immunoselective pressure.

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Section: Introductionmentioning

confidence: 99%

H-2 antigen expression: Loss in vitro, restoration in vivo, and correlation with cell-mediated cytotoxicity in a mouse lymphoma cell line

1978

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“…Data presented in Fig. 5 demonstrate that such treated thymus cells will not reveal any significant cytotoxic activity against the NKsensitive target Nulli but readily develop con- or chemical modifications introduced onto the surface of the EC target [9,52]. Under the conditions in our assays T cells seem unable to lyse the EC lines Nulli-SCC.…”

Section: Failttre Of Cotiveniional T Kilter Cells To Lyse Embryonal Cmentioning

confidence: 81%

T‐Cell Growth Factor Contains Activity that Supports Natural Killer Activity in Vitro

et al. 1983

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Lymphocytes from athymic and normal mice were tested and compared for cytotoxic activity after in vitro cultures supplemented with concanavalin A or T-cell growth factor (TCGF). Our results indicate that, in addition to cytotoxic T cells, natural killer (NK) activity can be recovered from lymphocytes cultured in the presence of TCGF and that this is not the result of contaminating interferon in the TCGF preparations. The NK nature of the effector cells was established by means of a panel of target cells, including a teratocarcinoma tumour cell, which enabled the distinction of T-cell- and NK-cell-mediated lysis.

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“…Non-neutralizing Abs (non-nAbs) can play a significant role in protection from infections caused by smallpox (64,65), Sindbis (66,67), yellow fever (68), influenza virus (69), Ebola virus (70), and Epstein-Barr virus–related cancer manifestation (71), supporting the rationale that non-nAbs hold great potential to be harnessed by an antiviral vaccine regimen. Among the non-neutralizing functions, Ab can provide protection from viral infection by mediating virolysis, phagocytosis, or ADCC through recruitment of complement factors and/or engaging Fc-receptor (FcR)–bearing cells.…”

Section: Non-neutralizing Antibodiesmentioning

confidence: 95%

HIV antibodies for treatment of HIV infection

Margolis

Koup

Ferrari

2017

Immunological Reviews

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Summary The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Further, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure.

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Cells that express viral antigens but lack H-2 determinants are not lysed by immune thymus-derived lymphocytes but are lysed by other antiviral immune attack mechanisms.

Cited by 63 publications

References 43 publications

H-2 antigen expression: Loss in vitro, restoration in vivo, and correlation with cell-mediated cytotoxicity in a mouse lymphoma cell line

H-2 antigen expression: Loss in vitro, restoration in vivo, and correlation with cell-mediated cytotoxicity in a mouse lymphoma cell line

T‐Cell Growth Factor Contains Activity that Supports Natural Killer Activity in Vitro

HIV antibodies for treatment of HIV infection

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