Functional Maturation of B Cell Repertoire Expression

Froscher, Barbara G.

doi:10.1007/978-1-4613-1873-6_6

Cited by 4 publications

(6 citation statements)

References 45 publications

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“…Further analysis [3] showed that 60% of these antibodies displayed a CTL-like MHC restriction, binding only to infected cells bearing class I antigens of the immunizing haplotype. Similar results have recently been reported by Froscher and Klinman [26] for mAb responses to SV-40 virus-transformed cells. We found that none of the 10 infected-cell-specific mAb generated in C57BL/6 mice after multiple injections of syngeneic, influenza-infected EL4 cells were restricted by the MHC in their recognition of the viral antigens.…”

Section: Discussionsupporting

confidence: 87%

“…These antibodies, like antigen receptors on the CTL, would be expected to be both MHC restricted and virus specific [l]. The possibility that MHC-restricted antibodies could be generated is supported by a number of recent reports in the literature [3,[24][25][26]. In particular, the study of the B cell responses to immunization with syngeneic, influenza-infected tumor cells by Wylie and Klinman [21] indicated that approximately two thirds of the anti-viral antibodies recovered in a splenic fragment assay of a primary response were specific for determinants present on infected cells but not on purified virus.…”

Section: Discussionmentioning

confidence: 97%

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Searching for MHC‐restricted anti‐viral antibodies: antibodies recognizing the nucleoprotein of influenza virus dominate the serological response of C57BL/6 mice to syngeneic influenza‐infected cells

1987

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An attempt has been made to generate monoclonal antibodies which recognize the same target structures on influenza-infected cells as those seen by cytotoxic T lymphocyte (CTL) receptors. Such antibodies, if they mimicked the T cell receptor specificity, would be expected to be both virus specific and restricted in their binding by the major histocompatibility complex (MHC) antigens. Approximately 200 hybridomas from C57BL/6 (H-2b) mice primed and boosted with influenza virus (X-31)-infected EL4 (a C57BL/6 T cell lymphoma) were screened for reactivity on infected and uninfected cells of different MHC haplotypes. Of the 10 hybridoma antibodies which were identified as being reactive with X-31-infected EL4, but not uninfected EL4, all reacted equally well with X-31-infected cells of H-2b, H-2d and H-2k haplotypes, indicating a lack of MHC restriction in their recognition of the infected cells. Unexpectedly, 7 of the 10 monoclonal antibodies were found to react specifically with the purified influenza virus nucleoprotein (NP), a predominant viral antigen in CTL recognition of infected cells. Fluorescence-activated flow cytometry confirmed that these antibodies were able to recognize NP serological determinants on the surface of viable, infected cells, but the anti-NP antibodies were unable to block the lytic activity of an NP-specific CTL clone.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 97%

Searching for MHC‐restricted anti‐viral antibodies: antibodies recognizing the nucleoprotein of influenza virus dominate the serological response of C57BL/6 mice to syngeneic influenza‐infected cells

1987

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“…4), whereas no effect was observed on two NP50-57-specific, Kk-restricted, T-cell hybridomas, HK9.5-24 and HK9.5-162 (Fig. 4 (12)(13)(14), whereas others have reported that their attempts have failed (15,16). More recently, a few anti-peptide/MHC antibodies have been reported (17)(18)(19).…”

Section: Resultsmentioning

confidence: 94%

A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells.

Andersen

Stryhn

Hansen

et al. 1996

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

127

106

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Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might lead to novel approaches in immunotherapy. However, it has proven difficult to generate antibodies with the specificity of T cells by conventional hybridoma techniques. Here we report that the phage display technology is a feasible alternative to generate antibodies recognizing specific, predetermined peptide/MHC complexes.T and B cells represent two fundamentally different recognition modes of the specific immune system. Through alternating selection processes T cells are educated to recognize antigenic peptides presented in association with self-molecules of the major histocompatibility complex (MHC) on the surface of antigen-presenting cells. In contrast, B cells are not educated to be self-MHC-restricted and B-cell receptors (antibodies), whether soluble or in membrane-bound form, recognize threedimensional target structures. The distinctly different education of B and T cells explains why antibodies with the MHCrestricted specificity of T cells are rare and why it has been difficult to generate such specificities by conventional B-cell hybridoma techniques. We have taken advantage of the selection power of the phage display technology which makes it possible to test tens of millions of individual clones and have devised a method to generate recombinant antibodies recognizing predetermined peptide/MHC complexes. The speed and feasibility of this method makes it realistic to produce antibodies to a variety of specific peptide/MHC complexes which may be useful in studying MHC-restricted T-cell recognition and may lead to novel approaches in diagnostics and immunotherapy.MATERIALS AND METHODS MHC Purification. The AKR mouse-derived lymphoma RDM-4 was used for Kk production as described (1). In brief, Kk molecules were immunoaffinity purified from detergent cell lysates by using the monoclonal anti-Kk antibody 11.4-1 (American Tissue Type Culture Collection). The affinity columns were washed extensively and bound MHC class I molecules were eluted with 0.05 M diethylamine, pH 11/0.15 M sodium chloride/0.1% sodium azide/0.1% sodium deoxycholate, neutralized, and concentrated by vacuum dialysis. Human 82-microglobulin was obtained from the urine of uremic patients and purified to homogeneity by gel filtration and chromatofocusing (1).The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.The influenza virus-derived nucleoprotein peptide NP50-57 (single-letter code, SDYEGRLI) and hemagglutinin peptide Ha255-262 (FESTGNLI) were synthesized manually on a RaMPS synthesizer (DuPont) using standard fluorenylmethoxycarbonyl protection strategy.Generation of Peptide/MHC Cl...

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“…Several (3-15) hours later, LNs and spleens were harvested from host mice; spleens were cut into small 1-mm cubes. The organs were cultured in DMEM supplemented with 10% ␥-globulin-free horse serum, glutamine, penicillin͞streptomycin, and neomycin for 7 days at 37°C in a 93% O 2 ͞7% CO 2 atmosphere; the culture medium was changed every other day (40). Single cell suspensions were made from the LNs and spleen fragments and stained with the appropriate This paper was submitted directly (Track II) to the PNAS office.…”

Section: Methodsmentioning

confidence: 99%

IL-7 is critical for homeostatic proliferation and survival of naïve T cells

Tan

Dudl

Leroy

et al. 2001

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

856

755

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In T cell-deficient conditions, naive T cells undergo spontaneous "homeostatic" proliferation in response to contact with self-MHC/peptide ligands. With the aid of an in vitro system, we show here that homeostatic proliferation is also cytokine-dependent. The cytokines IL-4, IL-7, and IL-15 enhanced homeostatic proliferation of naive T cells in vitro. Of these cytokines, only IL-7 was found to be critical; thus, naive T cells underwent homeostatic proliferation in IL-4(-) and IL-15(-) hosts but proliferated minimally in IL-7(-) hosts. In addition to homeostatic proliferation, the prolonged survival of naive T cells requires IL-7. Thus, naïve T cells disappeared gradually over a 1-month period upon adoptive transfer into IL-7(-) hosts. These findings indicate that naive T cells depend on IL-7 for survival and homeostatic proliferation.

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Functional Maturation of B Cell Repertoire Expression

Cited by 4 publications

References 45 publications

Searching for MHC‐restricted anti‐viral antibodies: antibodies recognizing the nucleoprotein of influenza virus dominate the serological response of C57BL/6 mice to syngeneic influenza‐infected cells

Searching for MHC‐restricted anti‐viral antibodies: antibodies recognizing the nucleoprotein of influenza virus dominate the serological response of C57BL/6 mice to syngeneic influenza‐infected cells

A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells.

IL-7 is critical for homeostatic proliferation and survival of naïve T cells

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