Structurally inherent antigenic sites. Localization of the antigenic sites of the α-chain of human haemoglobin in three host species by a comprehensive synthetic approach

Recently, the regions of myoglobin, which are recognized by T cells (T sites), were localized by a comprehensive synthetic strategy in which uniform synthetic overlapping peptides encompassing the entire protein chain were examined for stimulation of T cell proliferative activity. In this study, we report about the proliferative response to these peptides, as well as to the native protein, of lymph node cells from mice primed with the overlapping peptides either individually or in a mixture. Some, but not all, of the T site-containing peptides were effective in priming for an anti-myoglobin T cell response. Further, several peptides, which were highly immunogenic as free synthetic peptides, were not associated with any of the known T sites in this protein. Thus, the pattern of T cell recognition following priming with the overlapping peptides differs from the pattern observed when the native protein is the priming antigen. If antigen processing proceeds via fragmentation, then only those regions containing T sites would be expected to be effective in priming for a T cell response to the intact protein and, conversely, highly immunogenic peptides would correspond to T sites of the protein. Therefore, these findings indicate that the current concept of antigen fragmentation as a prerequisite for its presentation must be reappraised. We suggest that, in the presentation of a protein antigen, the protein is recognized predominantly intact and that the crucial aspects of presentation are determined by interaction with the cell membrane which trigger cellular activating events.

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“…Received January 31,1985; in revised form April 13,1985. The location of I-J gene(s) has become controversial.…”

Section: Discussionmentioning

confidence: 99%

Antigen presentation of myoglobin: profiles of T cell proliferative responses following priming with synthetic overlapping peptides encompassing the entire molecule

Bider

Atassi

1985

Eur J Immunol

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“…4). The procedure employed for the assignment of the sites has been described (13,14). Additional study will be required (32) to define the precise boundaries of the sites within the eight antigenic regions shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The amounts of 125I-labeled antibody bound were determined with a Beckman 4000 gamma counter. Titrations with five adsorbents of unrelated proteins and peptides [bovine serum albumin, sperm whale myoglobin, nonsense peptide (28), hemoglobin a-chain synthetic peptide [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] (14), and myoglobin synthetic peptide 87-100 (31)] were used as controls to correct for nonspecific binding.…”

Section: Methodsmentioning

confidence: 99%

Profile of the continuous antigenic regions on the extracellular part of the alpha chain of an acetylcholine receptor.

Mulac‐Jeričević¹,

Kurisaki²,

Atassi³

1987

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

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Reaction of overlapping synthetic peptides spanning the extracellular part (residues 1-210) of the a chain of the Torpedo californica acetylcholine receptor (an a28,8y pentamer) with anti-receptor antibodies produced the profiles of the continuous antigenic regions of the correlate segment. Essentially similar profiles were recognized by rabbit and outbred mouse antibodies against isolated receptor or mouse antibodies against membrane-bound receptor. The antigenic sites reside within eight continuous regions: residues 1-14, 25-36, 41-53, 63-75, 102-114, 128-138, 172-182, and 188-198. Five of these regions (the second and the fifth through the eighth) appeared to be immunodominant. Significantly, two of these antigenic regions (i.e., those residing within residues 128-138 and 188-198) coincided with known toxin-binding regions. The antigenic profile suggests that recognition is directed to the intact molecule and only very slightly to the processed (fragmented) protein.

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“…Also, as seen here and reported for hemoglobin a-chain (39), major antigenic sites could reside in surface regions that have very low hydrophilicity or are mostly hydrophobic. Such regions are rendered accessible by the three-dimensional and oligomeric characteristics ofa particular protein (39).…”

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confidence: 99%

Localization, synthesis, and activity of an antigenic site on influenza virus hemagglutinin.

Atassi¹,

Webster²

1983

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

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This paper reports the antigenicity of the fusion region of the influenza virus hemagglutinin (HA). Two peptides, comprising the fusion region (residues 1-11 ofthe HA2 part ofHA) ofstrain A and strain B influenza virus, were synthesized and their abilities to bind rabbit, goat, and human anti-influenza antibodies were determined. In addition, 30 anti-HA monoclonal antibodies were examined for their ability to bind the synthetic peptides. In quantitative immunoadsorbent titrations, the two peptides bound considerable amounts of antibodies in rabbit and goat antisera against virus or HA ofthe A or B strain as well as in several human sera from patients recovering from influenza A. Ofthe 30 anti-HA monoclonal antibodies, 5 bound completely and 4 bound partially to the peptides. Antibodies were raised in rabbits against the peptides by immunizing with peptide-bovine serum albumin conjugates or with the free peptides. Anti-peptide antibodies were bound by HA and by the intact virus ofthe respective strain. However, these antisera failed to exhibit significant virus neutralizing activity. In contrast, the monoclonal antibodies that reacted with these peptides inhibited viral infectivity. The results clearly show that residues 1-11 of HA2 represent an important antigenic site on influenza virus.The antigenicity ofinfluenza virus coat proteins, hemagglutinin (HA) and neuraminidase, has been the subject of great interest [for recent review see Webster et al. (1)]. Attention has been focused by the determination ofthe covalent structure ofseveral influenza HA variants, through sequence analysis of both the protein (2) and its cloned gene (for review, see ref.3) and, more recently, by the determination of the three-dimensional structure of the HA of influenza A virus by x-ray crystallography at 3-A resolution (4). The availability of this structural information permits attempts at elucidation of the immune responses to influenza virus at the molecular level. Localization and synthesis of the major antigenic and immunogenic sites of HA will afford peptides that may be used in an effective vaccination strategy. Also they should lead to the characterization of the type of antibody activity (i.e., whether neutralizing or non-neutralizing) elicited by each site and should permit an understanding of the effect of mutations on antigenic alterations.

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Structurally inherent antigenic sites. Localization of the antigenic sites of the α-chain of human haemoglobin in three host species by a comprehensive synthetic approach

Cited by 82 publications

References 39 publications

Antigen presentation of myoglobin: profiles of T cell proliferative responses following priming with synthetic overlapping peptides encompassing the entire molecule

Antigen presentation of myoglobin: profiles of T cell proliferative responses following priming with synthetic overlapping peptides encompassing the entire molecule

Profile of the continuous antigenic regions on the extracellular part of the alpha chain of an acetylcholine receptor.

Localization, synthesis, and activity of an antigenic site on influenza virus hemagglutinin.

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