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M Z Atassi

Publications and source records attributed to M Z Atassi.

At least 55 records · Page 3Linked to original sources
PubMed1993

Biological activities of rat antisera raised against synthetic peptides of human thyrotropin receptor.

Twenty three male Wistar rats were divided into five groups and were immunized with five overlapping synthetic peptides (Group I (n = 5), peptide 12-30; Group II (n = 5), 24-44; Group III (n = 4), 308-328; Group IV (n = 5), 324-344; and Group V (n = 4), 339-364) of human thyrotropin receptor (TSHR), which had been conjugated with rabbit serum albumin. Sera obtained 34 days after the first immunization were investigated for their ability to displace 125I-TSH binding to thyrotropin receptor (thyrotropin binding inhibitor immunoglobulins (TBII)). In addition, biological activity, namely thyroid stimulating (TSAb) or blocking (TSBAb) activities in them were tested with cultured porcine thyroid cells. TBII activities in Group I, II, III, IV, and V rats were 12.6 +/- 4.1% (range 9.2-17.2%), 16.3 +/- 4.0% (range 11.7-22.0%), 16.7 +/- 4.9% (range 13.2-20.1%), 14.5 +/- 5.7% (range 8.1-19.0%), and 13.8 +/- 6.3% (range 8.1-14.3%), respectively, which were not significantly different from control rat sera (12.3 +/- 6.7%, range 1.2-20.1%). TSAb activities in Group I, II, III, IV, and V rats were 608 +/- 675% (range 275-1813%), 234 +/- 26% (range 209-265%), 313 +/- 175% (range 187-568%), 190 +/- 63% (range 145-301%), and 134 +/- 24% (range 107-158%), respectively. TSAb activities in Group I, II, III, and IV rats were significantly higher than those from control rat sera (P < 0.01) while those of Group V were not significantly different from control rat sera. None of the rats in each group exhibited TSBAb activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Epitope-specific suppression of antibody response in experimental autoimmune myasthenia gravis by a monomethoxypolyethylene glycol conjugate of a myasthenogenic synthetic peptide.

A synthetic peptide corresponding to a myasthenogenic region of Torpedo californica acetylcholine (AcCho) receptor (AcChoR) alpha subunit, AcChoR alpha-(125-148), was conjugated to monomethoxypolyethylene glycol (mPEG). Injection of mice with the mPEG-AcChoR alpha-(125-148) conjugate and subsequent immunization with whole Torpedo AcChoR suppressed the development of experimental autoimmune myasthenia gravis (EAMG) by electrophysiological criteria. In anti-AcChoR sera from these animals, the antibody response against unconjugated AcChoR alpha-(125-148) was decreased, while the antibody responses against whole AcChoR and other epitopes were not altered. There were no detectable changes in T-cell proliferation responses to AcChoR alpha-(125-148) or to whole AcChoR in these animals. Prior injections with a "nonsense" peptide-mPEG conjugate had no effect on responses to the subsequent immunization with whole Torpedo AcChoR. The results indicate that the mPEG-AcChoR alpha-(125-148) conjugate has epitope-specific tolerogenicity for antibody responses in EAMG and that the AcChoR alpha-subunit region comprising residues 125-148 plays an important pathophysiological role in EAMG. The epitope-directed tolerogenic conjugates may be useful for future immunotherapies of human myasthenia gravis. The strategy of specific suppression of the antibody response to a predetermined epitope by using a synthetic mPEG-peptide conjugate may prove useful in manipulation and suppression of unwanted immune responses such as autoimmunity and allergy.

Amino Acid Sequence↗
PubMed1992

Biological activities of rabbit antibodies against synthetic human thyrotropin receptor peptides representing thyrotropin binding regions.

Recently, we have shown that the thyrotropin (TSH) binding regions of human thyrotropin receptor (TSHR) reside in two areas within residues 12-44 and 308-344. Serial antisera were raised against four overlapping synthetic peptides representing these two regions of TSHR (peptides 12-30, 24-44, 308-328, and 324-344) and were investigated for their ability to stimulate or block the cultured porcine thyroid cells. In addition, serum concentrations of triiodothyronine (T3) and thyroxine (T4) in serial sera obtained from each rabbit were examined. It was shown that residues of 12-30 and 324-344 of TSHR, respectively, are the site (at least a part of the site) where stimulating (TSAb) and blocking type (TSBAb) immunoglobulins are directed.

Amino Acid Sequence↗
PubMed1992

Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 113-120 (antigenic site 4) of myoglobin.

Immunochemical cross-reactivity of protein variants has been very frequently used to map protein antigenic sites. The approach is based on the assumption that amino acid substitutions affecting the binding of a protein to its antibody, particularly when monoclonal antibodies (mAbs) are used, must be part of the antigenic site and not far from it. The assumption was investigated in this study by determining the effects of amino acid substitutions outside the antigenic site on the reactivity of six myoglobin (Mb) variants with three mAbs of predetermined specificity prepared by immunization with a free synthetic peptide representing region 113-120 (antigenic site 4) of Mb. Two of the Mb variants used had no substitutions within residues 113-120 (the region to which the specificity of the mAbs is directed) and yet exhibited markedly decreased cross-reactions and binding affinities, relative to the reference antigen, sperm-whale Mb. The other three Mb variants possessed substitutions within, as well as outside, region 113-120 and showed very little cross-reactivities. The results of this study, particularly with the Mbs that have no substitutions within the indicated antigenic site, clearly show that substitutions outside the site, and which by design are not part of the site, can influence very markedly the reactivity of the protein variant with the anti-site mAbs. The approach can, therefore, lead to serious errors if used to identify residues of protein antigenic sites.

Amino Acid Sequence↗
PubMed1992

Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 145-151 (antigenic site 5) of myoglobin.

Monoclonal antibodies of predetermined specificity were prepared by immunization with a free (i.e., without coupling to any protein carrier) synthetic peptide representing region 145-151 of sperm whale myoglobin (SpMb) and their cross-reactions with eight Mb variants were determined. Five Mbs--bottle-nose dolphin myoglobin (BdMb), pacific common dolphin myoglobin (PdMb), horse myoglobin (HsMb), dog myoglobin (DgMb), and badger myoglobin (BgMb)--have an identical sequence in that region. Nevertheless, these Mbs exhibited very different cross-reactivities. BdMb and PdMb exhibited cross-activities which were comparable to that of the reference antigen, SpMb; while the reactivity of HsMb was remarkedly decreased, DgMb and BgMb showed almost no cross-reactions with these mAbs. Since the region 145-151 has an identical sequence in all the five Mbs, it is concluded that the differences in their antigenic reactivities with anti-region 145-151 mAbs are due to the effects of amino acid substitutions outside the region 145-151. Another pair of myoglobins, echidna myoglobin (EdMb) and chicken myoglobin (ChMb), have the same sequence in that region, but reacted very differently with anti-region 145-151 mAbs. The reactivity and affinity of EdMb were substantially decreased while those of ChMb were almost completely absent, relative to SpMb. It is concluded, contrary to popular assumptions, that when an amino acid substitution influences the binding of a protein variant to a mAb, it is not necessary for that substitution to be an actual contact residue (i.e., a residue within the antigenic site where the mAb binds). Such effects, which are often very drastic, could be due to indirect influences of the substitution on the chemical and binding properties of the site residues. Furthermore, residues which had been postulated, on the basis of these assumptions, to constitute discontinuous antigenic sites in SpMb, were found [from the present studies and those recently reported with mAbs against the other four antigenic site of Mb (regions 15-22, 56-62, 94-100, and 113-120 of SpMb)] to merely be exerting indirect effects on the known five antigenic sites of Mb. The effects of substitutions, which can happen even in the absence of conformational changes, are determined by many factors, such as the chemical nature of the substitution, its environment, its distance from the site, and the nature of the site residue(s) being affected.

Amino Acid Sequence↗
PubMed1992

Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 94-100 (antigenic site 3) of myoglobin.

Amino acid substitutions outside protein antigenic sites are very frequently assumed to exert no effect on binding to antiprotein antibodies, especially if these are monoclonal antibodies (mAbs). In fact, a very popular method for localization of residues in protein antigenic sites is based on the interpretation that whenever a replacement causes a change in binding to antibody, then that residue will be located in the antigenic site. To test this assumption, mAbs of predetermined specificity were prepared by immunization with a free (i.e., without coupling to any carrier) synthetic peptide representing region 94-100 of sperm whale myoglobin (Mb). The cross-reactivities and relative affinities of three mAbs with eight Mb variants were studied. Five Mb variants which had no substitutions within the boundaries of the designed antigenic site exhibited remarkable, and in two cases almost complete, loss in cross-reactivity relative to the reference antigen, sperm whale Mb. Two myoglobins, each of which had one substitution within region 94-100, showed little or no reactivity with the three mAbs. It is concluded that substitutions outside an antigenic site can exert drastic effects on the reactivity of a protein with mAbs against the site and that caution should be exercised in interpreting cross-reactivity data of proteins to implicate residues directly in an antigenic site.

Amino Acid Sequence↗
PubMed1992

Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 15-22 (antigenic site 1) of myoglobin.

Monoclonal antibodies (mAbs) of predetermined specificity were prepared by immunizing with a free (i.e., not conjugated to any carrier) synthetic peptide representing region 15-22 (site 1) of sperm whale myoglobin (SpMb). The cross-reactions of Mb variants with three mAbs were studied in order to determine whether such interactions are influenced by substitutions outside the site. Finback whale Mb, which has no substitutions within region 15-22, showed lower cross-reactivity and relative binding affinity than the reference antigen, SpMb. Bottle-nose Atlantic dolphin myoglobin (BdMb) and badger myoglobin (BgMb), although they have identical substitutions within region 15-22 (Ala-15 to Gly and Val-21 to Leu), showed very different binding properties. The cross-reaction of BdMb was quite comparable to that of SpMb, while that of BgMb was much lower. Since the two proteins have identical structures in regions 15-22, the differences in their cross-reactivities are readily attributed to the effects of substitutions outside this region. Another pair of myoglobins, horse myoglobins (HsMb) and chicken myoglobin (ChMb), also have two identical substitutions (Ala-15 to Gly and Val-21 to Ile) within region 15-22, but possessed different cross-reactivity. The results indicate that the reaction of mAbs, whose specificity is precisely known and predetermined by the immunizing free peptide, can be markedly affected by substitutions outside the indicated binding region on the protein.

Amino Acid Sequence↗
PubMed1992

Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 56-62 (antigenic site 2) of myoglobin.

This work was carried out in order to study the effects of substitutions outside antigenic site 2 of sperm whale myoglobin (SpMb) on the reactivity of protein variants with antisite 2 monoclonal antibodies (mAbs). A synthetic peptide corresponding to region 56-62 (site 2) of SpMb was used as an immunogen in mice in its free form (i.e., without coupling to any carrier) to prepare a panel of mAbs whose predetermined specificity is directed, by design, against this region. The binding of three of these mAbs to eight Mbs from different species was studied. Myoglobins of Pacific common dolphin, finback whale, and horse, which have no substitutions within region 56-62 relative to SpMb, showed remarkable differences in their cross-reactivities and relative affinities with each of the mAbs. Myoglobins of badger, chicken, and dog, although they have an identical substitution within the site (Ala-57 to Gly), exhibited cross-reactivities with a given mAb that were affected differently. Echidna Mb, which has one replacement (Glu-59 to Ala) within region 56-62, displayed greatly reduced cross-reactivities and relative binding affinities. The results, especially those from Mbs that have no substitutions within the boundaries of site 2, clearly indicate that substitutions outside site 2 of Mb can exert drastic effects on the binding of the Mb variants with mAbs whose specificity was predesigned to be against the site. These indirect effects and their impact on site reactivity will completely explain previous findings on cross-reactivities of Mb variants with mAbs of unknown specificity and will rule out the postulations of discontinuous sites in Mb, which were based on the assumption that every substitution affecting reactivity is directly involved in binding to antibody.

Amino Acid Sequence↗
PubMed1992

Profile of the regions on the alpha-chain of human acetylcholine receptor recognized by autoantibodies in myasthenia gravis.

Eighteen synthetic overlapping peptides encompassing the entire extracellular part (residues alpha 1-210) of the alpha-chain of human acetylcholine receptor (AChR) and a 19th peptide (residues alpha 262-276) corresponding to an extracellular connection between two transmembrane regions were prepared and used for the measurement, by solid-phase radioimmunoassay, of the binding of autoantibodies in plasma from myasthenia gravis (MG) patients. Autoantibodies were found to recognize only a limited number of the synthetic peptides. The regions recognized resided predominantly within the areas alpha 10-30, alpha 111-145 and alpha 175-198 and, less frequently, region alpha 45-77. Differences in the recognition profile of the peptides from patient to patient indicated that the autoantibody responses were under genetic control. However, by using a mixture of the appropriate peptides, it was possible to determine autoantibodies in all 15 myasthenia sera and to distinguish between these, normal human sera and other neurological or autoimmune diseases. The mapping of the continuous antigenic regions recognized by autoantibodies on the alpha-chain of human AChR has permitted a comparison of the regions recognized by autoantibodies and autoimmune T-cells from the same donor. It also provided a peptide-based direct antibody binding method for diagnosis of MG.

Adolescent↗
PubMed1992

HIV envelope protein is recognized as an alloantigen by human DR-specific alloreactive T cells.

Recent studies from this laboratory reported the mapping of the full profile of T-cell allorecognition regions of HLA-DR2 beta subunit. The results indicated the presence of an allodeterminant within DR2 beta regions 141-156. In another study, we have shown that this allodeterminant is one of five regions of structural homology between the DR2 beta molecule and the HIV-envelope protein gp120 region 254-268. The fact that gp120 peptide 254-268 is homologous to the allodeterminant within the DR2 beta region 141-156 prompted us to investigate whether synthetic gp120 peptide 254-272 is recognized by human DR2-specific alloreactive T-cell lines. Five human alloreactive T-cell lines were prepared that were specific for the DR2 molecule and did not recognize DR1. These lines mounted in vitro proliferative responses to the allodeterminant peptide DR141-156 and also responded to the DR-similar peptide gp254-272. Removal of the residues 262-272 from the gp120 peptide (i.e., peptide 254-263) resulted in essentially complete loss of its proliferative activity. The effect of deletion of three residues of homology (Val-Val-Ser) at the N terminal (i.e., peptides DR145-156 and gp257-272) was examined. Peptide DR2 beta 145-156 exhibited very low stimulating activity, whereas peptide gp 257-272 did not cause T-cell proliferative responses in any of the alloreactive T-cell lines. The T-cell lines did not respond to unrelated peptide controls, thus further confirming the specificity of these responses. These findings indicate that the virus is recognized as an alloantigen by human alloreactive DR2-specific T cells.

Amino Acid Sequence↗
PubMed1991

Localization and synthesis of the hormone-binding regions of the human thyrotropin receptor.

Two regions of human thyrotropin (thyroid-stimulating hormone, TSH) receptor (TSHR) (residues 12-44 and 308-364) were selected on the basis that they exhibit no sequence resemblance to luteinizing hormone/chorionic gonadotropin receptor. Five synthetic overlapping peptides (12-30, 24-44, 308-328, 324-344, and 339-364) were studied for their ability to bind 125I-labeled human TSH (hTSH), its isolated alpha and beta subunits, bovine TSH, ovine TSH, human luteinizing hormone, and human follicle-stimulating hormone. The human TSHR peptides 12-30 and 324-344 exhibited remarkable binding activity to human, bovine, and ovine TSH and to the beta chain of hTSH. Lower binding activity resided in the adjacent overlapping peptides, probably due to the contribution of the shared overlap to the binding. The specificity of TSH binding to these peptides was confirmed by their inability to bind human luteinizing hormone, human follicle-stimulating hormone, and the alpha chain of hTSH. Thyrotropins did not bind to bovine serum albumin or to peptide controls unrelated to the TSHR system. Furthermore, the binding of hTSH to TSHR peptides 12-30 and 324-344 was almost completely (approximately 90%) inhibited by rabbit antibodies against hTSH but not by antisera against unrelated proteins. It is concluded that the binding of TSH to its receptor involves extensive contacts and that the TSHR peptides 12-30 and 324-344 contain specific binding regions for TSH that might be either independent sites or two faces (subsites) within a large binding site.

Amino Acid Sequence↗
PubMed1991

The short-neurotoxin-binding regions on the alpha-chain of human and Torpedo californica acetylcholine receptors.

The continuous regions for short-neurotoxin binding on the alpha-chains of Torpedo californica (electric ray) and human acetylcholine receptors (AChR) were localized by reaction of 125I-labelled cobrotoxin (Cot) and erabutoxin b (Eb) with synthetic overlapping peptides spanning the entire extracellular part of the respective alpha-chains. On Torpedo AChR, five Cot-binding regions were found to reside within peptides alpha 1-16, alpha 23-38/alpha 34-49 overlap, alpha 100-115, alpha 122-138 and alpha 194-210. The Eb-binding regions were localized within peptides alpha 23-38/alpha 34-49/alpha 45-60 overlap, alpha 100-115 and alpha 122-138. The main binding activity for both toxins resided within region alpha 122-138. In previous studies we had shown that the binding of long alpha-neurotoxins [alpha-bungarotoxin (Bgt) and cobratoxin (Cbt)] involved the same regions on Torpedo AChR as well as an additional region within residues alpha 182-198. Thus region alpha 182-198, which is the strongest binding region for long neurotoxins on Torpedo AChR, was not a binding region for short neurotoxins. On human AChR, peptide alpha 122-138 possessed the highest activity with both toxins, and lower activity was found in the overlap alpha 23-38/alpha 34-49/alpha 45-60 and in peptide alpha 194-210. In addition, peptides alpha 100-115 and alpha 56-71 showed strong and medium binding activities to Eb, but low activity to Cot, whereas peptide alpha 1-16 exhibited low binding to Cot and no binding to Eb. Comparison with previous studies indicated that, for human AChR, the binding regions of short and long neurotoxins were essentially the same. The finding that the region within residues alpha 122-138 of both human and Torpedo AChR possessed the highest binding activity with short neurotoxins indicated that this region constitutes a universal binding site for long and short neurotoxins on AChR from various species.

Acetylcholine↗
PubMed1991

Paucity of humoral response in patients to glioma-associated antigen(s): antigen localization by immunofluorescence.

Xenogeneic immunization of freshly-prepared human glioma extracts into goats has yielded a polyclonal antiserum, which after multiple absorptions specifically identifies antigenic entities only in glioma extracts, and not in appropriate controls, both by radioimmunoassays (RIAs) and Western immunoblots. The results from the absorbed polyclonal antiserum have been confirmed by the successful generation of six stable murine monoclonal antibodies (MAbs) which recognize a subset of the same antigens with high specificity on immunoblots and with no apparent cross-reactivities by RIA to normal brain, serum, liver, muscle, kidney, spleen, or melanoma tissues. Moreover, the tested murine MAbs (B12C4) reveal a striking and abundant glial filament protein, possibly related to glial fibrillary acidic protein (GFAP) or other intermediate filament proteins, by frozen-section immunofluorescence. This is seen only in gliomas and is absent, or dramatically reduced, in normal human cortex. Use of potent immortalizing strain (FF41) of Epstein-Barr virus (EBV) to establish antibody-secreting human lymphoblastoid lines, and the generation of mouse-human chimeric fusions, have yielded lines possessing variable supernatant human antibody secretion. Radioimmunoassays using culture supernatants, and sera from glioma patients and an normal individual, have demonstrated surprisingly similar reactivity profiles, even after a sensitive sandwich RIA employing the B6C6 murine MAb. These results suggest that, although human glioma-associated antigens, including possibly the up-regulation of GFAP expression, clearly exist, there seems to be a muted humoral response as evidenced by a paucity of tumor-specific B-cells. This may be due to antigenic shielding by the blood-brain barrier, or due to a form of immunological compromise in patients harboring these malignancies.

Antibodies, Neoplasm↗
PubMed1991

Preparation and characterization of antisera and of murine monoclonal antibodies to human glioma-associated antigen(s).

Human glioma-associated markers can be exploited for the development of new diagnostic strategies and treatment modalities for these malignancies. A goat antiserum was first raised against human anaplastic astrocytoma (AC or AA) and glioblastoma multiforme (GB or GBM) extracts. Extensive sequential absorptions with normal brain tissue, normal serum, and human serum albumin (HSA) gave an antibody fraction specific for glioma. Balb/c mice were subsequently immunized with these glioma extracts. B-cell hybridomas from these mice were then cloned and subcloned by limiting dilution, yielding six monoclonal antibodies (MAbs) that were entirely specific for tumor tissues, and did not react with normal human serum or with normal human brain, liver, kidney, spleen, or muscle. Moreover, the murine MAbs did not cross-react with certain other human tumors, including melanoma. The fully absorbed antiserum and the murine MAbs both identify a polypeptide pattern possibly related to human glial fibrillary acidic protein (GFAP) or other intermediate filament proteins on immunoblots. These immunological reagents could serve as powerful tools for the diagnosis and possibly therapy of these uniformly fatal tumors.

Animals↗
PubMed1991

Synthesis of tolerogenic monomethoxypolyethylene glycol and polyvinyl alcohol conjugates of peptides.

Recent studies from this laboratory showed that tolerogenic peptide conjugates are very effective reagents for obtaining epitope-specific immunosuppression of antibody responses to immunopathogenic sites on multideterminant complex protein antigens. This paper describes the procedure for synthesis of well-defined conjugates of peptides to monomethoxypolyethylene glycol (mPEG) or to polyvinyl alcohol (PVA). The first step involves succinylation of the hydroxyl groups on the polymers by reaction with succinic anhydride. The polymer is then coupled via the carboxyl of the succinyl group to the alpha-NH2 of the completed peptide on the synthetic resin, while maintaining intact all the side-chain protecting groups on the peptide. The mPEG or PVA-peptide conjugates are cleaved from the resin and purified by standard procedures. This method results in the preparation of conjugates in which one molecule of tolerogenic polymer is coupled to the N-terminal of an otherwise unaltered peptide molecule.

Amino Acid Sequence↗
PubMed1990

Mapping of the full profile of T cell allorecognition regions on HLA-DR2 beta subunit.

Alloreactive human T cell lines were developed by repeated in vitro restimulation with alternate allogeneic cells of similar DR2 serotype, but differing at other HLA loci. These polyclonal T cells recognized DR specificities in common with all DR2 serotypes. The allorecognition profiles of DR2 beta by the T cell lines were mapped by consecutive uniform-sized overlapping peptides encompassing the entire extracellular and intracellular regions of the DR beta subunit. It was found that the T cell allorecognition sites are focused around the first and third polymorphic regions of the N-terminal domain, and interestingly, include conserved areas in the DR beta second domain as well as the intracellular segment beta 222-237. These findings have important implications for allorecognition. Comparison with the previous analysis of antibody-binding regions of DR2 beta revealed some similarities and differences in the antibody and T cell alloresponses to this histocompatibility antigen.

Amino Acid Sequence↗
PubMed1990

Characteristics of peptides which compete for presented antigen-binding sites on antigen-presenting cells.

The T cell recognition of globular protein antigens requires the cell surface presentation of the protein by Ia-expressing antigen-presenting cells (APC). The mechanisms by which APC function remain to be elucidated. To gain a better understanding of association of antigen with APC surfaces, a large panel of peptides of diverse physicochemical properties was assayed for the ability to compete with presented antigen for binding sites on the APC surface. Competition was measured by the ability of a peptide to block the I-Ek-restricted T cell response to pigeon cytochrome c (Pc) as presented by APC. The panel assayed included overlapping peptides representing the entire length of sperm whale myoglobin and the alpha and beta chains of human adult hemoglobin as well as synthetic conformational peptides of lactate dehydrogenase C4 exhibiting stable secondary, alpha-helical structures. The results presented here show that several peptides of this group compete with the presented form of Pc for binding sites on the APC. However, there is no single biochemical property or amino acid sequence algorithm which predicts the blocking ability. The peptides which compete with presented Pc are not predicted to assume the amphipathic alpha-helical conformation hypothesized by De Lisi and Berzofsky (Proc. Natl. Acad. Sci. USA 1986. 82: 7048) for T cell antigenic peptides. However, peptides designed and synthesized to adopt a stable alpha-helical secondary structure show more potent blocking activity than the corresponding linear peptides, suggesting that the secondary structure may indeed be a contributing factor in the ability of presented antigenic peptides to be bound by the APC. The results with the myoglobin and hemoglobin peptides show no connection between any particular secondary structure of the peptide in the native proteins and the ability of the peptides to block presentation. Further, there is no correlation between the major histocompatibility complex restriction of the competing peptides and their ability to block the I-Ek-restricted Pc-specific T cell response. This suggests that antigen presented by the APC may be bound to APC structures other than Ia prior to association with Ia. Such additional binding sites for presented antigen may be necessary to facilitate association with Ia.

Amino Acid Sequence↗