T Cell Recognition of Lysozyme Iv. Localization and Genetic Control of the Continuous T Cell Recognition Sites by Synthetic Overlapping Peptides Representing the Entire Protein Chain

Bixler, Garvin S.; Yoshida, Takeshi; Atassi, M. Zouhair

doi:10.1111/j.1744-313x.1984.tb00819.x

Cited by 31 publications

(11 citation statements)

References 54 publications

(51 reference statements)

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“…The results reported here show that LNCs whose specificity is directed against a region [a- (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)] that is completely buried within the subunit association surfaces in Hb recognize the free synthetic peptide and the isolated subunit but not the intact tetramer. LNCs against regions that are only partially involved in subunit association or against exposed regions that are not involved at all in subunit contacts recognize the peptide and the isolated subunit as well as intact Hb.…”

Section: Resultsmentioning

confidence: 80%

“…Several years ago, studies from this laboratory showed that T-cell epitopes on a protein very frequently overlap or coincide with B-cell epitopes that occupy exposed surface regions ofthe protein (10,11,(29)(30)(31)(32)(33)(34)(35). These regions, therefore, are prime targets for proteolysis and would be expected to be readily destroyed by processing (27,36).…”

Section: Resultsmentioning

confidence: 99%

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T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing.

Atassi

Yoshioka

Bixler

1989

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

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Processing of a protein antigen into fragments is believed to be a prerequisite for its presentation by the antigen-presenting cell to the T cell. This model would predict that, in oligomeric proteins, T cells prepared with specificity for regions that are buried within subunit asiation surfaces should recognize the respective regions in vitro equally well on the isolated subunit or on the oligomer. Three hemoglobin (Hb) a-chain synthetic peptides, corresponding to areas that are situated either completely [a-(31-45)] or partially [a-(41-45) and a-(81-95)] within the interface between the a and fi subunits of Hb, and a fourth peptide representing a completely exposed area in tetrameric Hb were used as immumogens in SJL/J (H-2') mice. Peptide-primed T cells were passaged in vitro with the respective peptide to obtain peptide-specific T-lymphocyte lines. T-cell clones were isolated from these lines by limiting dilution. T-cell lines and clones that were specific for buried regions in the subunit association surfaces recognized the free peptide and the isolated subunit but not the Hb tetramer. On the other hand, T cells with specificity against regions that are not involved in subunit interaction and are completely exposed in the tetramer recognized the peptide, the isolated subunit, and the oligomeric protein equally well. The responses of the T-cell lines and clones were major histocompatibility complex-restricted. Since the same x-irradiated antigen-presenting cells were employed, the results could not be attributed to differences or defects in Hb processing. The findings indicate that in vitro the native (unprocessed and undissociated) oligomeric protein was the trigger of major histocompatibility complex-restricted T-cell responses.The presentation of a protein antigen to T lymphocytes is believed to be dependent on a first step in which the protein is internalized and processed into fragments that reappear on the surface of the antigen-presenting cell (APC) and are presented in association with major histocompatibility complex (MHC) molecules to the T cell (1, 2). Although there have been reports that a protein molecule is presented intact by the APC (see Discussion), the idea that processing is a prerequisite for presentation is by far the most widely accepted model. Many consequences of this model can be predicted and tested. If protein fragments and not the intact protein are presented by the APC to the T cell, it would be expected that T cells that are specific for the subunit interface in an oligomeric protein (if such T cells could be made) should recognize the isolated subunit or the oligomer equally well. Obviously, the T-cell recognition site cannot remain buried (in the interface between the subunits) after the oligomer is processed into fragments. If, on the other hand, these T cells recognize the peptide and the isolated subunit but not the oligomer, then this would be indicative that the subunit interface has remained buried in an intact oligomeric protein.In this paper we report the ro...

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Section: Resultsmentioning

confidence: 80%

Section: Resultsmentioning

confidence: 99%

T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing.

Atassi

Yoshioka

Bixler

1989

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

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“…Nine different HEL peptides reported to be restricted to either H-2 b , H-2 d or H-2 q MHC II haplotypes (11,32) were synthesized by the Stanford Peptide Synthesis Group. Three peptides, HEL 20 -35 restricted to H-2 b , HEL 106 -116 restricted to H-2 d , and HEL 93-113 restricted to H-2 q , were chosen based immunogenicity as assessed in lymph node proliferation assays of immunized untransplanted control mice.…”

mentioning

confidence: 99%

Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow

Tsao

Allen

Logronio

et al. 2009

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

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Antigen-specific immune responses are impaired after allogeneic hematopoietic cell transplantation (HCT). The events contributing to this impairment include host hematolymphoid ablation and donor cell regeneration, which is altered by pharmacologic immune suppression to prevent graft-versus-host disease (GVHD). A generally accepted concept is that graft T cell depletion performed to avoid GVHD yields poorer immune recovery because mature donor T cells are thought to be the major mediators of protective immunity early post-HCT. Our findings contradict the idea that removal of mature donor cells worsens immune recovery post-HCT. By transplantation of purified hematopoietic stem cells (HSC) compared with bone marrow (BM) across donor and recipient pairs of increasing genetic disparity, we show that grafts composed of the purified progenitor population give uniformly superior lymphoid reconstitution, both qualitatively and quantitatively. Subclinical GVHD by T cells in donor BM likely caused this lymphodepleting GVHD. We further determined in the major histocompatibility complex (MHC)-mismatched pairs, that T cell restricted proliferative responses were dictated by donor rather than host elements. We interpret these latter findings to show the importance of peripheral antigen presentation in the selection and maintenance of the T cell repertoire.immune reconstitution ͉ mice ͉ T cell selection

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“…It is well established that, in the immune responses to a multi-determinant complex protein antigen, the responses to each determinant (both antibody and T cell) are under separate genetic control (Okuda et aL, 1979;Twining et a/, 1981;David and Atassi, 1982). In a given mouse strain, the regions on a protein antigen that are recognized by antibodies and * by T cells may coincide but there might also be regions on the protein that are recognized by antibodies and for which no detectable T-cell responses are found and/or conversely Tcell recognition regions for which no antibodies are detectable (Bixier and Atassi, 1983, 1984ab, 1985Atassi, 1984;Bixler et aL, 1984). In both Balb/c and SJL, peptides L1, 12 and C-tail were most protective against BgTX poise,t'Žng (PI: Balb/c, 3.2; SJL, 2.5-2.7).…”

Section: Discussionmentioning

confidence: 99%

“…For proliferative assay, single cell suspensions of LNC from primed mice were prepared in Hank's balanced salt solution. The cells were washed and resuspended in RPMI 1640 with 1% normal mouse serum and supplemented as described (Bixler et aL, 1984). The number of viable cells was determined by vital staining with fluorescein diacetate (Rotman and Papermaster, 1966 2.7.…”

Section: Radioimmunoadsorbent Titrations Of Anti-bgtx Antiseramentioning

confidence: 99%

Molecular Recognition of Alpha-Neurotoxins

Atassi¹

1990

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T Cell Recognition of Lysozyme Iv. Localization and Genetic Control of the Continuous T Cell Recognition Sites by Synthetic Overlapping Peptides Representing the Entire Protein Chain

Cited by 31 publications

References 54 publications

T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing.

T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing.

Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow

Molecular Recognition of Alpha-Neurotoxins

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