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PubMed1984

Identification of distinct predominant epitopes recognized by myoglobin-specific T cells under the control of different Ir genes and characterization of representative T cell clones.

We characterized the fine specificity of antigen recognition of myoglobin-immune T cells from B10.D2, B10.GD, and B10.A(5R) mice. Polyclonal H-2d T cells show a predominant response to an epitope centering on Glu 109 and His 116. These residues localize a dominant epitope to one segment of the myoglobin surface, but probably are not the only amino acid residues involved. This response pattern maps genetically to I-Ad (or Kd) based on the B10.GD recombinant strain. A different epitope specificity was detected in B10.A(5R) T cells mapping to I-E beta b E alpha k or I-Cd, but no difference was detected between strains differing at the Igh locus. Thus, epitope specificity varied with Ia haplotype but not Igh allotype. Myoglobin-specific B10.D2 T cell lines were established, and five clones specific for the Glu 109, His 116 epitope were isolated; these were all restricted to I-Ad antigen-presenting cells. These clones represent the dominant specificity in the polyclonal T cell response to myoglobin and will be useful in characterizing the structure and function of T cell receptors for antigen and Ia. The differences in number and nature of T cell epitopes compared to B cell epitopes of myoglobin are discussed.

Animals↗
PubMed1984

Topologic mapping of protective and nonprotective epitopes on the variant surface glycoprotein of the WRATat 1 clone of Trypanosoma brucei rhodesiense.

Monoclonal antibodies were used in competitive antibody binding assays to define and map epitopes on the variant surface glycoprotein of the WRATat 1 clone of T. b. rhodesiense. By using a panel of 30 WRATat 1-specific monoclonal antibodies, 16 epitopes were defined that fall into four clusters, having 1, 1, 3, and 11 distinct epitopes respectively. All epitopes were easily classified as being 1) exposed uniformly on the surface of the trypanosome, 2) exposed only in the region of the flagellar pocket, or 3) "buried", based on the ability or inability of the monoclonal antibodies to bind living trypanosomes in a fluid phase immunofluorescence assay. Monoclonal antibodies that bind exposed surface epitopes are protective, whereas only three of seven that bind exclusively to flagellar pocket epitopes are protective. None of the nine monoclonal antibodies that recognize buried epitopes are protective. Also, antibody-mediated immunity to WRATat 1 trypanosomes is not associated with any particular subclass of antibody. The IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA subclasses each contain examples of protective monoclonal antibodies.

Animals↗
PubMed1984

Epitopes in myelin basic protein reactive with monoclonal antibodies.

The epitopes (antigenic determinants) evoked by guinea pig or monkey myelin basic protein (BP) for 7 monoclonal antibodies (MAb) have been localized to 4 different sequences of the BPs extracted from various species. The first pair of epitopes is included within residues 1-14 and reacts with 2 rat IgG MAbs having slightly different specificities. The second pair of epitopes overlap within the sequence 86-100, requiring the Phe(91)-Phe(92) residues. One includes only residues 90-100 and reacts with a rat IgG MAb, the other is longer and reacts with a mouse IgM MAb. The third epitope lies within residues 114-124 (specifically including the single Trp) and reacts with a rat IgG MAb. A cross-reacting epitope in the amino half of the molecule is present in certain species (human, bovine and guinea pig). The fourth pair of epitopes includes residues 131-140 and is severely species-restricted. A mouse IgM MAb reacts practically only with guinea pig BP. Another IgG MAb reacts with human, chimpanzee, monkey, bovine and rat-18.5 kDa BPs, to a much lesser extent with rabbit and rat-14 kDa BPs and not with guinea pig, pig or chicken BPs. A cross-reacting epitope in the amino half of the molecule may be present in the more reactive species.

Animals↗
PubMed1995

Selection of tumor-specific epitopes on target antigens for radioimmunotherapy of breast cancer.

Evidence is presented for two different breast epithelial antigens that some epitopes have greater tumor specificity and are more effective targets for radioimmunotherapy than others. The two antigens, which are major components of the human milk fat globule membrane, are breast mucin and a M(r) 46,000 glycoprotein (BA46). Of five monoclonal antibodies (Mc5, Mc1, BrE-1, BrE-2, and BrE-3) against breast mucin, all recognize overlapping amino acid epitopes on the tandem repeat domain. However, each have unique and different tissue and tumor specificities and unique epitope structures on the fully glycosylated breast mucin. In preclinical studies, radioimmunoconjugates of all five monoclonal antibodies inhibit growth of transplantable breast tumors in immunodeficient mice. In human clinical trials, radioiodinated Mc5 was very poor in localizing breast tumor metastases. On the other hand, 111In-labeled BrE-3 imaged almost 90% of breast tumors and showed promise in radioimmunotherapy when labeled with 90Y. The failure of Mc5 in clinical trials may be partly attributed to the high levels of its epitope on circulating mucin compared to the epitope of BrE-3. The Mc5 binding affinity increased significantly with glycosylation, while the BrE-3 epitope was masked by glycosylation. The BA46 glycoprotein is a breast tumor-associated membrane antigen containing an NH2-terminal, epidermal growth factor-like domain into which a cell adhesion sequence (RGD) is inserted and a COOH-terminal domain with homology to the phospholipid binding C1/C2 domain of coagulation factors V and VIII. It promotes cell attachment in an RGD-dependent manner. Monoclonal antibody Mc8, which binds to the C2-like domain, is only moderately effective in experimental radioimmunotherapy, while Mc3, which binds an epitope in the EGF-like RGD domain, was highly effective in destroying breast tumors in nude mice. With 90Y-labeled Mc3, 6 of 7 mice are cured of the tumors. These results indicate that by selecting appropriate monoclonal antibodies, a normal antigen can be used as a target for radioimmunotherapy.

3T3 Cells↗
PubMed1994

Definition of encephalitogenic and immunodominant epitopes of guinea pig myelin basic protein (Gp-BP) in Lewis rats tolerized neonatally with Gp-BP or Gp-BP peptides.

Two distinct epitopes of guinea pig basic protein (Gp-BP), residues 72-89 and 87-99, possess encephalitogenic activity in Lewis rats. The purpose of this study was to determine to what degree the 87-99 epitope functions in rats that have been injected with whole Gp-BP, and whether additional epitopes in Gp-BP are encephalitogenic. To address these questions, we induced neonatal tolerance to the dominant synthetic (S)72-89 peptide or to the combination of both S72-89 and S87-99 peptides, and evaluated resistance to experimental autoimmune encephalomyelitis (EAE) induced by Gp-BP, as well as T cell responses to peptides that encompassed most of the Gp-BP molecule. The results demonstrated that virtually all of the encephalitogenic activity of Gp-BP resides within the two described encephalitogenic epitopes. Moreover, deletion of responses to the dominant epitopes prompted T cell responses to other nonencephalitogenic epitopes of Gp-BP, a pattern of response observed previously in rats that had recovered from EAE and in those protected from EAE by vaccination with TCR peptides. These data may have relevance to human autoimmune diseases such as multiple sclerosis in that naturally or immunologically regulated responses to dominant epitopes that are likely to be encephalitogenic may be obscured by increased responses to relatively innocuous determinants of basic protein. Elevated responses to potentially pathogenic autoantigens will likely involve both types of determinants, thus, underscoring the importance of distinguishing encephalitogenic from nonencephalitogenic determinants.

Amino Acid Sequence↗
PubMed1994

Distribution of carbohydrate epitopes among disjoint subsets of leech sensory afferent neurons.

Carbohydrate recognition plays an important role in the development of normal projections of sensory afferent neurons in the leech CNS. Four different carbohydrate epitopes are expressed by sensory afferents on their 130 kDa surface proteins: all sensory afferents share a common carbohydrate epitope (CE0) that helps them to enter and project diffusely across the synaptic neuropil; a restricted expression of three other carbohydrate epitopes (CE1, CE2, and CE3) serves to distinguish three subsets of sensory afferents. We examined the subsets of sensory afferents defined by their subset carbohydrate epitopes in the leech lip, skin, gut, and CNS. We established that the CE1, CE2, and CE3 subset epitopes define disjoint subsets of neurons by double labeling sensory afferents with monoclonal antibodies for different pairs of subset epitopes. We found that CE2 and CE3 afferents populate the lip and skin, but not the gut, and that these two subsets of sensory afferents have convergent projection patterns in the CNS. We found that CE1 afferents populate the gut and skin, but not lips; furthermore, their CNS projections diverge from those of CE2 and CE3 afferents. Our data fit the hypothesis that these carbohydrate epitopes are related to sensory modality of afferent subsets.

Animals↗
PubMed1995

Isotype-associated recognition of allergen epitopes and its modulation by antigen dose.

The existence of competing and blocking IgG antibodies and their interrelationship with IgE antibodies was investigated in the IgE immune response of CBA/J mice to bee venom phospholipase A2 (PLA2) and keyhole limpet haemocyanin (KLH). Minute doses of antigen induced high titres of both IgE and IgG antibodies, whereas large doses elicited high IgG responses but only weak IgE antibody titres. Immunization with minute doses of antigen led to the production of antibodies with class-associated epitope specificities (designated epitopes G for IgG and E for IgE antibodies), and therefore no competition was observed. For IgG antibody production, G epitopes were immunodominant and IgG antibodies directed to E epitopes were produced only after immunization with an increased immunogen dose. Under this condition IgG antibodies recognizing the E epitopes acted as blocking antibodies competing with IgE antibodies for binding to E epitopes, the immunodominant epitopes for the IgE response. The data demonstrate the existance of distinct immunodominant antigenic determinants for IgE and IgG antibodies on PLA2.

Animals↗
PubMed1993

In vitro selection of RNA epitopes using autoimmune patient serum.

Nucleotide-specific autoimmune epitopes have not been precisely defined despite the fact that certain kinds of DNA and RNA species are known to bind autoantibodies. Our laboratory has used nucleic acid epitope libraries, consisting of randomized RNA pools, to select specific RNA conformers recognized by antibodies, including a peptide-specific antibody. In the present study, serum from a patient with systemic lupus erythematosus was used to select ligands from an RNA epitope library. The selected RNA contained sequences that were found to be similar to regions within the U1 small nuclear RNA, previously shown to react with autoantibodies. Furthermore, the selected RNA epitopes were able to inhibit autoantibody reactivity with specific regions of U1 RNA, thus demonstrating their immunologic cross-reactivity with the natural RNA epitope. Although the origins of nucleic acid-binding autoantibodies are not understood, the identification of these defined U1 RNA epitopes, in regions of the RNA where cell proteins are not known to bind, is most compatible with models of immunologic cross-reactivity or with direct presentation to the immune system rather than with anti-Id models. These experiments demonstrate that RNA epitope libraries may be used to reveal the fine specificity of autoimmune recognition and provide a useful approach to study RNA-protein interactions.

Base Sequence↗
PubMed1993

Analysis of the epitopes of proliferating cell nuclear antigen recognized by monoclonal antibodies.

BACKGROUND: Monoclonal antibodies to proliferating cell nuclear antigen (PCNA) are increasingly used for evaluation of cell proliferation especially in diagnostic pathology. To understand the different staining characteristics of such antibodies, we found it important to map the reactive epitopes in detail. EXPERIMENTAL DESIGN: Overlapping, synthetic 15-mer peptides encoding the entire PCNA amino acid sequence were analyzed for reactivity with 6 anti-PCNA monoclonal antibodies using enzyme-linked immunosorbent assay and flow cytometric competition analysis. One immunodominant region was studied using a set of peptides with single amino acid substitutions. Further epitope localization was obtained by immunoblotting of fusion protein constructs. RESULTS: The epitopes recognized by the antibodies could be assigned to specific peptides. Five monoclonal antibodies (19A2, 19F4, TO17, TO30, PC10) reacted with the same protein region (aa 111-125) whereas one antibody (TOB7) recognized a separate region of the protein (aa 181-195). The reactivity pattern with 8 recombinant PCNA-fusion proteins agreed with the peptide data. The immunodominant aa 111-125 peptide reactive antibodies differed concerning immunofluorescence patterns. These differences could be attributed to epitope microheterogeneity within this peptide as determined by reactivity with Ala-substituted peptides. The 19A2, 19F4 and PC10 antibodies showed nuclear fluorescence and similar but not identical peptide recognition patterns. Compared with 19A2 and 19F4, the PC10 antibody was directed against a simpler epitope. TO17 and TO30 gave cytoplasmic filamentous staining and their epitopes were different from those defined by the other monoclonal antibodies. CONCLUSIONS: The results indicate that induced anti-PCNA antibodies recognize well defined linear epitopes, in contrast to PCNA autoepitopes which are strongly dependent on the protein conformation.

Amino Acid Sequence↗
PubMed1996

Allergenic and antigenic determinants of latex allergen Hev b 1: peptide mapping of epitopes recognized by human, murine and rabbit antibodies.

BACKGROUND: The rubber elongation factor in Hevea rubber (Hev b 1) is one of the most important latex allergen and is leading cause of latex type 1 hypersensitivity in children with spina bifida. OBJECTIVE: The aim of this study was to define the allergenic and antigenic epitopes of Hev b 1. METHODS: The immunoglobulin- (Ig)E and IgG antibody binding sites on Hev b 1 allergen were delineated by enzyme linked immunosorbent assay (ELISA) using synthetic overlapping peptides covering the whole Hev b 1 sequence. In order to improve the binding capacity and specificity all peptides were biotinylated at the N-terminal end via a 6-aminohexanoic acid as spacer and then adsorbed to streptavidin pre-coated microtitre plates. Fine mapping to define the essential amino acid residues for the antibody binding was achieved by using overlapping peptides with one amino acid offset. RESULTS: It was demonstrated that the IgE epitopes were located in different regions of Hev b 1 including the C-terminal segment (121-137) and the segments with amino acid residues of 30-49 and 46-64. Two monoclonal antibodies (MoAbs) II2F3 and II4G9 raised against purified Hev b 1 recognized the C-terminal segment only. The results of epitope mapping with three rabbit antisera revealed that five positive peptides, including the epitope peptides 31-49, 46-64 and 121-137, were involved in the antibody-binding sites. Fine mapping on the segments 46-64 and 121-137 showed that the two MoAbs reacted with the peptide 125-134 in the C-terminal region, whereas the peptide with amino acids 124-134 was essential for recognition by human IgE antibodies. Epitopes to rabbit polyclonal IgG and human IgE were also found to be involved in the amino acid residues of 47-59. CONCLUSION: Our results indicate that the most allergenic/antigenic portions of Hev b 1 allergen are the C-terminal region and the region with amino acid residues of 31-64. In both regions, the minimal IgE-binding epitope is almost identical with the IgG-binding epitope.

Allergens↗
PubMed1996

Immunodominance analysis of CTL responses to influenza PR8 virus reveals two new dominant and subdominant Kb-restricted epitopes.

In the present study, a systematic analysis of the influenza (Flu) PR8 determinants recognized by H-2b mice was undertaken. A single Db-restricted immunodominant epitope (NP(366)) was previously known in this system. Twenty-three different Flu PR8-derived peptides that bound either Kb or Db molecules in vitro were identified. Sixteen were immunogenic following peptide immunization of C57BL/6 mice, yet CTL induced by peptide immunization recognized PR8-infected target cells only in the case of the NP(366) and NS2(114) epitopes. Similarly, CTL responses following whole-PR8 virus immunization were detected only for the same two determinants. CTL recognizing these dominant epitopes had high avidity for peptide-pulsed target cells, with 5 to 200 pM of peptide required for 30% specific lysis. In contrast, most (80%) of the remaining epitopes were recognized with lower avidity (30% effective concentration in the range of 0.4-50 nM). Repeated in vitro stimulation of primary CTL cultures revealed one additional Kb-restricted epitope (M1(128)). This peptide bound Kb with high affinity (4.6 nM) and induced CTL that effectively recognized PR8-infected cells. These results suggest that 1) this epitope is produced by natural processing in relatively high amounts and 2) low precursor frequency might be related to the subdominant status of the M1(128) epitope. Taken together, these results illustrate the crucial contributions of MHC-binding capacity, and T cell repertoire availability, to the shaping of the repertoire of CTL specificities for Flu Ag virus.

Animals↗
PubMed1996

Monoclonal antibody O10 defines a conformationally sensitive cell-surface epitope of proteolipid protein (PLP): evidence that PLP misfolding underlies dysmyelination in mutant mice.

Mutations in the gene for proteolipid protein (PLP) have been associated with CNS dysmyelination and abnormal oligodendrocyte death in spontaneous mouse mutants and in Pelizaeus-Merzbacher disease; however, the effect of mutations on PLP structure and function are little understood. We have identified a monoclonal antibody directed against a novel cell surface epitope of PLP, termed O10. By immunofluorescence analysis, COS-7 cells transiently transfected to express PLP (or its isoform DM20) can be stained with antibody O10 and another antibody (A431) directed against the C terminus of PLP/DM20. The subcellular distribution of immunofluorescence labels for the two antibodies is not identical, suggesting that the O10 epitope is acquired post-translationally. When PLP/DM20 from jimpy, jimpymsd, and rumpshaker mutant mice is expressed in COS-7 cells and compared with wild-type PLP/DM20, none of the mutant isoforms displays the O10 epitope, whereas the C-terminal epitope is detected. Because the O10 but not the A431 epitope is also sensitive to SDS and reducing agents, this strongly suggests abnormal protein folding in the PLP mutants. PLP from jimpymsd mice is obviously misfolded, because the amino acid substitution (Ala242 --> Val) is located within a transmembrane domain to which the O10 antibody does not bind. We propose that the O10 epitope emerges as the full length protein reaches a functional tertiary structure and that the absence of this epitope marks a structural defect of PLP that leads to dysmyelination.

Animals↗
PubMed1997

B-cell epitopes recognized by IgE from patients sensitive to Amb a 5.

BACKGROUND: The response to allergens characterized by IgE-mediated hypersensitivity is selective. The search for the inherited contribution to atopy has among other things, focused on the linkage of sensitivity to the presence of specific alleles in the DR and DQ locus. More than 90% of the responders to Amb a 5, an allergen from ambrosia artemisifolia, are DR-2 positive. This relationship is logically linked to the T-cell epitope presentation by the HLA complex. OBJECTIVES: This study aims to investigate a possible relationship between T-cell epitopes, B-cell epitopes and the alleles of the DR and DQ loci in Amb a 5 sensitive DR-2+ and DR-2- individuals. METHODS: Inhibition of solid state Elisa assays by IgE-enriched and IgG-depleted, heated sera. The inhibition was carried out in checkerboard pattern, bidirectionally; A inhibits B and B inhibits A. RESULTS: The B-cell epitopes defined by the inhibition pattern were all found to be conformational. Three different epitope patterns (A, B, C) were recognized. The IgE and IgG complexes were found in only one responder. The DR and DQ locus alleles were all sequenced. Although all the individuals studied responding to Amb a 5 show presence of alleles such as 1501, associated with DR-2, our data indicates no correlation between the B-cell epitopes recognized and the DR and DQ locus alleles. A well known, general T-cell motif was recognized in the known sequence of Amb a 5. CONCLUSIONS: Our investigation suggests that the choice of B-cell recognition is regulated independently of a putative link between T-cell epitope recognition and the D locus.

Adult↗
PubMed1998

Polyclonality and multispecificity of the CTL response to a single viral epitope.

The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28-39 in hepatitis B surface Ag was defined to explore the immunologic constraints on mutational escape from the CTL response during a viral infection. Using a panel of hepatitis B surface Ag residue 28-39-specific CTL clones, the response to this epitope was found to be extremely diverse at the level of TCR fine specificity and beta-chain usage. Although each clone recognized shared as well as unique residues within the epitope as TCR contact sites, even the shared residues were recognized differently by different TCRs. Despite these differences, all clones were comparably cytolytic following Ag stimulation and produced similar amounts of antiviral cytokines previously shown to inhibit HBV replication. These results demonstrate that the CTL response to individual viral epitopes can be markedly polyclonal and multispecific, such that mutational inactivation of a single TCR contact site will not usually lead to viral escape from all CTL clones of the same epitope specificity. Given these constraints and the fact that the CTL response is usually directed against several different epitopes during most viral infections, mutational inactivation of a single epitope is not likely to be sufficient to cause viral persistence.

Amino Acid Substitution↗
PubMed1998

Comparison of coat protein epitopes of two zucchini yellow mosaic virus isolates.

Serological differences between two zucchini yellow mosaic virus (ZYMV) isolates (ZYMV-169 and ZYMV-M) obtained from two distinct geographical locations in Japan were determined by mapping epitopes on the coat proteins (CPs) of the two isolates. A total of 45 monoclonal antibodies (MAbs) against the two isolates were produced and the epitopes on the CPs were delineated by reacting these MAbs with trypsin-treated ZYMV particles and Escherichia coli-expressed ZYMV CP fragments. Six MAbs of groups I-a and I-b, specific for ZYMV-169, recognised two epitopes in the N-terminal region at amino acids (aa) 1-28 and 6-41 of ZYMV-169 CP. Fourteen MAbs of group II, specific for ZYMV-M, recognised epitopes in the N-terminal region of ZYMV-M CP. Twenty-one MAbs of groups III-a, III-b(i), III-b(ii), and III-b(iii), reacting with both isolates, recognised four epitopes; one epitope was located in the N-terminal region at aa 6-28 and the remaining three epitopes were located in the core region at aa 42-95, 171-227 and 228-259 of ZYMV CPs.

Amino Acid Sequence↗
PubMed1999

Association of antibiotic treatment-resistant Lyme arthritis with T cell responses to dominant epitopes of outer surface protein A of Borrelia burgdorferi.

OBJECTIVE: To explore further the association of antibiotic treatment-resistant Lyme arthritis and T cell reactivity with outer surface protein A (OspA) of Borrelia burgdorferi, including the identification of T cell epitopes associated with this treatment-resistant course. METHODS: The responses of peripheral blood and, if available, synovial fluid lymphocytes to B burgdorferi proteins, fragments, and synthetic peptides, as determined by proliferation assay and interferon-gamma production, were compared in 16 patients with treatment-responsive and 16 with treatment-resistant Lyme arthritis. RESULTS: The maximum severity of joint swelling correlated directly with the response to OspA. Moreover, the only significant difference between patients with treatment-resistant and treatment-responsive arthritis was in reactivity with N-terminal and C-terminal fragments of OspA, OspA1 (amino acids [aa] 16-106), and OspA3 (aa 168-273). Epitope mapping showed that 14 of the 16 patients with treatment-resistant arthritis had responses to OspA peptides (usually 4 or 5 epitopes), whereas only 5 of the 16 patients with treatment-responsive arthritis had reactivity with these peptides (usually 1 or 2 epitopes) (P = 0.003). Patients with HLA-DRB1 alleles associated with treatment-resistant arthritis were more likely to react with peptide 15 (aa 154-173) and, to a lesser degree, with peptide 21 (aa 214-233) than patients with other alleles, whereas the responses to other epitopes were similar in both groups. CONCLUSION: The maximum severity of joint swelling and the duration of Lyme arthritis after antibiotic treatment are associated with T cell responses to specific epitopes of OspA.

Adolescent↗
PubMed2005

Validation of in silico prediction by in vitro immunoserological results of fine epitope mapping on citrate synthase specific autoantibodies.

In silico antibody-antigen binding predictions are generally employed in research to rationalize epitope development. These techniques are widely spread despite their technical limitations. To validate the results of these bioinformatic calculations evidence based comparative in vitro studies are necessary. We have used a well-conserved mitochondrial inner membrane antigen-citrate synthase to develop a model for comparative analysis of the predicted and the immunoserologically verified epitopes of circulating autoantibodies. Epitopes were predicted using accepted tools: the GCG Wisconsin package and TEPITOPE 2000. An overlapping multipin ELISA assay--covering 49% of the citrate synthase molecule--was developed to map autoantibody epitopes of individuals (healthy, systemic autoimmune, and heart transplanted) in different immunopathological conditions. From the 40 synthesized decapeptides 34 were predicted in silico and 27 were validated in vitro. Thirty-two percent of epitopes were recognized by majority of sera 47% by at least one sera. False positive predictions were 21%. There was major difference in the recognized epitope pattern under different immunopathological conditions. Our results suggest that special databases are needed for training and weighing prediction methods by clinically well-characterized samples, due to the differences in the immune response under different health status. The development of these special algorithms needs a new approach. A high number of samples under these special immunological conditions are to be mapped and then used for the "fine tuning" of different prediction algorithms.

Amino Acid Sequence↗
PubMed2000

B-cell epitopes of the envelope glycoprotein of caprine arthritis-encephalitis virus and antibody response in infected goats.

Goats infected with caprine arthritis-encephalitis virus (CAEV) develop high titres of antibodies to Env. Not only is no consistent neutralizing response found but anti-Env antibodies have even been associated with disease in infected goats. To identify the continuous antigenic determinants involved in this atypical anti-Env response, we mapped CAEV-CO Env by screening an epitope expression library with infected goat sera. In addition to the four previously described epitopes, seven novel antigenic sites were identified, of which five were located on the surface (SU) and two in the transmembrane (TM) subunits of Env. The SU antibody-binding domains located in the variable regions of the C-terminal part of the molecule (SU3 to SU5) showed the strongest reactivity and induced a rapid seroconversion in six experimentally infected goats. However, the response to these immunodominant epitopes did not appear to be associated with any neutralizing activity. The pattern of serum reactivity of naturally infected goats with these epitopes was restricted, suggesting a type-specific reaction. Interestingly, the reactivity of peptides representing SU5 sequences derived from CAEV field isolates varied with the geographical and/or breeding origin of the animals. This suggests that peptides corresponding to the immunodominant SU epitopes may well be useful in the serotyping of CAEV isolates. Furthermore, the identification of the CAEV Env epitopes will permit us to functionally dissect the antibody response and to address the role of anti-Env antibodies either in the protection from or in the pathogenesis of CAEV infection.

Amino Acid Sequence↗