T-cell recognition and antigen presentation of myoglobin. Protein recognition by site-specific T-cell clones is influenced by amino acid substitutions outside the site

Yoshioka, M; Atassi, M. Zouhair

doi:10.1042/bj2580645

Cited by 4 publications

(6 citation statements)

References 35 publications

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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: 85%

“…It has been shown that site-specific T-cell recognition of myoglobin is influenced by amino acid substitutions outside of the site itself (41,42). These substitutions were distant in sequence from the site but close to it in the 3-dimensional structure.…”

Section: Resultsmentioning

confidence: 99%

“…The results cannot be explained by competition for Ia between homologous regions on the a and ( chains of Hb. The buried region a- (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) shows very poor homology to the ,3 chain. In fact the homology of the exposed region a-(51-65) to the 13 chain (residues [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70]) is quite high (9 of 15 residues, with one segment of 5 residues).…”

Section: Resultsmentioning

confidence: 99%

“…In fact the homology of the exposed region a-(51-65) to the 13 chain (residues [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70]) is quite high (9 of 15 residues, with one segment of 5 residues). Therefore, if there were to be competition for Ia, it will more likely happen with region a-(51-65) and not with a- (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Therefore, the lack of recognition of Hb by anti-[a-(31-45)] T cells is not caused by the region's homology to the (3 chain, but rather by its inaccessibility in the Hb tetramer.…”

Section: Resultsmentioning

confidence: 99%

“…These substitutions were distant in sequence from the site but close to it in the 3-dimensional structure. Since the site-specific clones were obtained by repeated passage with peptide (42), it is difficult to visualize how environmental residues, which themselves are not directly involved in binding, could influence recognition unless the intact protein was the presented species.…”

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: 85%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

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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Autoimmune T cell recognition of human acetylcholine receptor: the sites of T cell recognition in myasthenia gravis on the extracellular part of the α subunit

et al. 1990

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Autoimmune T cell lines were prepared from peripheral blood lymphocytes of five myasthenia gravis patients by passage in vitro with an equimolar mixture of 18 overlapping synthetic peptides corresponding to the entire extracellular region (residues alpha 1-210) of the alpha subunit of human acetylcholine receptor (AChR). The proliferative responses of the human AChR-specific T cell lines to each of the individual peptides were determined. It was found that the profiles of the peptides recognized by the T cells were different among the five T cell lines, consistent with genetic control operating at the recognition site level. However, other regulatory influences may play important roles in the triggering of the autoimmune responses. These results suggest that the pathogenesis of this autoimmune disease is variable at the cellular-molecular level.

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Presynaptic and postsynaptic neurotoxins. Investigation of the structures of the immune recognition sections

1998

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This paper discusses literature reports over the last 12 years and the results of our own experimental investigations of the structures of the immune recognition regions of protein antigens --in particular presynaptic and postsynaptic neurotoxins from spider and snake venoms.Of the more than 3000 species of spiders [1] and about 2340 species of snakes [2] living in the world, hundreds are poisonous. The organic parts of the venoms of these animals contain protein components with various molecular masses that consist mainly of enzymes and toxins. The roles of the majority of these enzymes remain unelucidated, while the toxins are the active principles of the venoms, which is expressed in their binding to elements of the presynaptic or postsynaptic membranes. The toxins binding to presynaptic membranes are classified into three groups: 1) those directed to the channels and neuromuscular receptors; 2) blockers of neuromuscular excitation; and 3) so-called "pure" presynaptic stimulatory toxins acting on the plasmatic membranes of nerve endings. The first group includes toxins active not only in the presynaptic compartment but also in the neurons. Some of them --for example, /3-bungarotoxin --besides affecting the channels and receptors, act as proteolytic or lipolytic enzymes modifying the structures of the membranes near their specific binding sections [3]. On the other hand, the neurotoxins of the second group, blockers of neuromediator excitation, such as botulin and tetanus toxin, are highly specific. The active subunits of these toxins are directed through the plasmatic membrane to the cytoplasm of the nerve endings, where they block the release of the mediator by an as yet unexplained mechanism. The third group, of "pure" presynaptic toxins, such as latrotoxin, act on the plasmatic membranes of nerve endings, promoting the generation of interterminal signals, which in the final account leads to a massive stimulation of the release of the neuromediator [4].Postsynaptic neurotoxins binding to nicotinic acetyicholine receptors are defined as o~-neurotoxins, tx-Neurotoxin molecules, which contain from 65 to 74 amino acid residues and 5 intramolecular disulfide bonds (long neurotoxins) or 60-62 residues with 4 disulfide bonds (short neurotoxins), bind specifically to nicotinic acetylcholine receptors in postsynaptic membranes and block the channel-openingffunction of cholinergic ligands. To determine the interrelationship between these activities requires an all-sided investigation of the structural and conformational, and also the immunochemical, features of the binding regions in the toxin and receptor molecules.Since the determination of the primary structure of an ~-neurotoxin (toxin a from the cobra Naja nigrocollis) [5], a fairly large number of reports have been published in which the relationship between the structure and functions of neurotoxins is considered [6][7][8][9][10]. On the other hand, functional investigations of the acetylcholine receptor, the tx-subunit of which is responsible for binding ace...

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T-cell recognition and antigen presentation of myoglobin. Protein recognition by site-specific T-cell clones is influenced by amino acid substitutions outside the site

Cited by 4 publications

References 35 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.

Autoimmune T cell recognition of human acetylcholine receptor: the sites of T cell recognition in myasthenia gravis on the extracellular part of the α subunit

Presynaptic and postsynaptic neurotoxins. Investigation of the structures of the immune recognition sections

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