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At least 1,225 records · Page 68Linked to original sources
PubMed1994

Alloreactive feature of HLA-DP-specific cytotoxic T-cell clone.

The alloreactive feature of CD4+ cytotoxic T-cell clone that could specifically lyse the cells bearing DPB1*0202 sequence was described. The clone was generated from a mixed culture of peripheral blood lymphocytes derived from siblings who were HLA-A, B, C, DR, and DQ identical by serological typing and whose DNA sequence of the second exon of DPB1 was one-allele mismatched by oligonucleotide typing (responder, PDB1*0201/0402; stimulator, DPB1*0202/0402). Specific cytotoxic activity of the clone was strictly limited against the cells bearing DPB1*0202 and was not able to lyse the other tested cells bearing DPB1*0201, 0301, 0401, 0501, 0601, 0901, 1301, and 1601. The cytotoxic activity of the clone was blocked by treatment of target cells with anti-DP monoclonal antibodies (B7/21). On the other hand, treatment of target cells with blocking agents of endogenous or exogenous antigen transport pathway (brefeldin A (BFA), endogenous; chloroquine, exogenous) had no effect on the cytotoxic activity of the clone. These results strongly favor the view that the DP epitopes recognized by the clone are conformational epitopes conferred by specific amino acids in hypervariable regions of the HLA-DP second DPB1 exon and the contribution of peptides in the HLA grooves to the conformational epitope motif is less likely.

Acyclovir↗
PubMed1996

Establishment and characterization of an anti-idiotypic CD4+ CD8- T cell line to murine anti-alpha(1 --> 3) dextran antibody.

It is known that anti-alpha(1 --> 3) dextran antibodies of BALB/c mice are ordinarily of distinctive idiotypes (Id), one of which is the individual idiotype (IdI) that is represented by J558 or M104E to myeloma protein. In the present study, we established T cell line of Th1 type which recognized the Id of anti-alpha(1 --> 3) dextran antibody, and investigated its specificity and functions. The T cell line, named J-2R, had a phenotype of CD3+ CD4+ CD8- and expressed alphabeta-T cell receptors (TcR). J-2R proliferated in response to J558 in an I-Ed-restricted manner but did not respond to M104E which had substitution at amino acids 100 and 101. We confirmed that J-2R recognized J558 IdI, using synthetic peptides corresponding to two serial amino acid residues, Arg100 and Tyr101, spanning the J558 IdI in the third hypervariable region (hv3) of the heavy chain. alpha(1 --> 3) dextran-binding B cells which were isolated from dextran-immunized mice activated J-2R, but B cells from nonimmune mice did not. J-2R produced IL-2, IFN-gamma and IL-6, but did not produce IL-4, IL-5, or IL-10. Furthermore, J-2R inhibited the growth of J558 myeloma cells inoculated to the syngeneic mice in vivo. These findings suggest that Id-specific CD4+ T cells, J-2R, are involved in Id network and may play a role in vivo. J-2R is useful for analysis of the role of the Id-specific helper T cells in immune network because J558 IdI is frequently present on anti-alpha(1 --> 3) dextran antibodies.

Amino Acid Sequence↗
PubMed1996

American trypanosomosis: in situ and generalized features of parasitism and inflammation kinetics in a murine model.

American trypanosomiasis: In situ and generalized features of parasitism and inflammation kinetics in a murine model. Experimental Parasitology 83, 267-274. Mimicking the natural conditions of mammalian infection, metacyclic trypomastigote forms of a Mexican isolate (Ninoa) of Trypanosoma cruzi were inoculated into mice in order to study inflammation kinetics and parasite clearance at the inoculation site, parasite tropism to different organs, and local inflammatory cell infiltrates. Polymorphonuclear cells were detected at the inoculation site as early as 1 hr after inoculation. Peak cell infiltrate was observed at 24 hr; at 96 hr polymorphonuclear cells had disappeared. Mononuclear cell infiltrates began at 24 hr, peaking at Day 15, and then stared disappearing by Day 30. Antigens and parasites were detected by conventional techniques up to 15 min and thereafter became undetectable. Amplification of the hypervariable region of kinetoplast minicircle DNA by polymerase chain reaction was positive from 24 hr to Day 15, and the reaction became negative on Day 30. Myositis was observed in skeletal muscle from Days 7 to 180, it progressed from slight to severe, with an inflammation process which included macrophages, plasmatic cells, and a few eosinophils, the phenotype of the infiltrating cells included LyT2+ and LyT1+ on Day 30, and both cell populations decreased in parallel on Day 180. Antigen and parasite nests were present from Day 15 to 180; in muscle the earliest time at which minicircle DNA was detected was Day 7 and it was present until Day 180. Myocarditis was also observed; it developed from slight to severe in between Days 7 and 30, then gradually decreased, and cleared up. Mononuclear cell infiltrates in the myocardium were present from Days 7 to 180. Antigen and parasite nests were detected at Days 15 and 30 and disappeared at Day 180, although minicircle DNA was detected until the last day of observation. Both skeletal and heart muscles showed inflammatory reaction foci containing T. cruzi antigen. There was twice the number of foci in heart as in skeletal muscle. This ratio was maintained by Day 30; later skeletal muscle showed persistent inflammation which was practically cleared up in the heart. Parasites or antigen were not detected by Day 180 in both skeletal and cardiac muscle; however, minicircle DNA was amplified, indicating that an small proportion of parasites evaded immune response. According to these data, Mexican Ninoa Strain has a classification as biodeme 3.

Amino Acid Sequence↗
PubMed1997

Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes.

Because Wolfram (or DIDMOAD) syndrome is supposed to be a mitochondrial (mt)-mediated disease, we investigated a group of eight DIDMOAD patients with respect to point mutations of the mtDNA thus far described as being associated with defined mitochondrial disorders such as MELAS, MERRF, and LHON. Furthermore, to screen DIDMOAD patients for other mtDNA defects we used Southern blot analysis to detect mtDNA length mutations and rearrangements as well as PCR-SSCP and direct sequencing to screen all ND genes (complex I of the respiratory chain), the 22 tRNAs, and a part of the cyt b gene for unknown mutations. As a disease control group, 17 LHON patients (harboring one of the primary LHON mutations) were included in this study because of the overlapping clinical symptoms (optic atrophy) in both syndromes. We compared mtDNA variants identified in DIDMOAD patients with those found in LHON patients as well as in a control group consisting of 67 healthy German blood donors. In total, the control group was characterized by 29 polymorphic sites in ND and tRNA genes that define certain major Caucasian haplotypes. We found that a cluster of nucleotide exchanges at nucleotide positions (nps) 4216 and 11,251 roughly discriminates controls (12/67 controls, 18%) from the disease groups (6/8 DIDMOAD patients, 75%; 10/17 LHON patients, 59%). All 4216-positive LHON patients (10 patients) were concentrated in a haplogroup defined by additional exchanges at nps 10,398, 12,612, and 13,708 (haplogroup A), while the bulk of 4216-positive DIDMOAD patients (5 patients) were found in a distinct haplogroup consisting of nucleotide exchanges at nps 4917, 10,463, 13,368, 14,233, and 15,928. The frequencies of both haplogroups were significantly lower in the control group versus the respective disease groups. A more detailed analysis was performed by sequencing the two hypervariable regions of the non-coding D-loop region from patients and controls and corroborated the ranging in the two major haplogroups. Thus, the different clinical features of the mitochondrial disease groups investigated here corresponded to different clusters of mtDNA variants, which might act as predisposing haplotypes, increasing the risk for disease.

Adult↗
PubMed1994

Antibodies to complementary peptides as probes for receptors.

Peptide hormones initiate their physiological responses by binding to receptor proteins embedded in the plasma membranes of their target cells. Mechanisms accounting for specific protein-protein interactions, such as peptide hormone binding by cell receptors or epitope binding by antibody have not been defined. A fundamental tenet of the immunological network hypothesis is the generation of anti-idiotypic antibodies to epitopes located in the hypervariable regions of antibody evoked in the same animal species. Anti-idiotypic antibodies to antibodies to peptide hormones with specificity for epitopes involving antibody binding sites may mimic the actions of the peptide hormone by binding to receptors and evoke cell responses associated with the hormone. A provocative relationship was identified in the genetic code, which recognized that complementary codons for strongly hydrophobic amino acids code for strongly hydrophilic amino acids. This led to the proposal and then to demonstration that peptide pairs based on the nucleotide sequences of complementary codons bind one another. It was then proposed that immunization with complementary peptides to peptide hormones may produce antibodies which, analogous to anti-idiotypic antibodies, may mimic the hormone. Some antibodies to complementary peptides for peptide hormones have been shown to mimic the peptide hormones by binding to their receptors and evoking cell responses characteristic of those of the hormones. Exploiting these relationships, some antibodies to complementary peptides for peptide hormones have been used to identify, purify, and characterize receptor proteins for peptide hormones. Polypeptide hormones initiate their characteristic physiologic effects by binding to specific receptor proteins located on the plasma membranes of their target cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1999

A conformationally-constrained MHC class II I-Ag7-derived peptide protects NOD mice from the development of diabetes.

Allele-specific peptide vaccination against disease-associated MHC class II molecules is a promising new strategy for modulating self-antigen presentation to autoreactive T cells in autoimmune diseases. To evaluate the potential of this approach for treatment of insulin-dependent diabetes mellitus (IDDM), we have designed a cyclic peptide vaccine, DiavaX, from the third hypervariable region of the beta-chain of the NOD mouse MHC class II I-Ag7. NOD mice were treated at 5 and 9 weeks of age with 100 microg DiavaX emulsified in alum, a control peptide in alum, or alum alone. At the end of the study, 87% of alum treated mice had developed diabetes, compared with only 28% of DiavaX-treated mice. None of the control peptides, including a linear I-Ag7, a scrambled cyclic I-Ag7, or an analogous cyclic I-Aspeptide, reduced the incidence of diabetes, demonstrating that the protective effect of DiavaX is conformationally dependent and both allele- and sequence-specific. DiavaX treatment did not cause any general immune suppression, but did induce peptide-specific antibodies and memory T cells. DiavaX-induced protection from diabetes was associated with the maintenance of a non-destructive islet-associated autoimmune response. These data indicate that a conformationally constrained peptide from the disease-associated MHC represents a potential vaccine candidate for the prevention of clinical IDDM.

Amino Acid Sequence↗
PubMed1994

Structural mimicry and enhanced immunogenicity of peptide epitopes displayed on filamentous bacteriophage. The V3 loop of HIV-1 gp120.

The principal neutralizing determinant of the human immunodeficiency virus type 1 (HIV-1) is an intra-chain disulphide-bridged loop, designated V3, in the third hypervariable region of the surface glycoprotein gp120. Peptide sequences from the V3 loop of gp120 from HIV-1 strain MN (HIV-1MN) were engineered into the N-terminal region of the major coat protein of filamentous bacteriophage fd, leading to their display in multiple copies on the surface of the bacteriophage virion. Peptides displayed in this way were shown to be remarkably effective structural mimics of the natural epitope. They were recognised by human HIV antisera and evoked high titres of antibodies in mice, which cross-reacted with other strains of HIV and were capable of neutralizing the virus. In addition, antibody production could be stimulated by simultaneous inoculation with T-cell epitopes similarly displayed on filamentous bacteriophage. The bacteriophage display system offers a powerful means of studying the immunological recognition of proteins and is a promising vaccine model.

Amino Acid Sequence↗
PubMed1997

Three-dimensional structure of an Fab-peptide complex: structural basis of HIV-1 protease inhibition by a monoclonal antibody.

F11.2.32, a monoclonal antibody raised against HIV-1 protease (Kd = 5 nM), which inhibits proteolytic activity of the enzyme (K(inh) = 35(+/-3)nM), has been studied by crystallographic methods. The three-dimensional structure of the complex between the Fab fragment and a synthetic peptide, spanning residues 36 to 46 of the protease, has been determined at 2.2 A resolution, and that of the Fab in the free state has been determined at 2.6 A resolution. The refined model of the complex reveals ten well-ordered residues of the peptide (P36 to P45) bound in a hydrophobic cavity at the centre of the antigen-binding site. The peptide adopts a beta hairpin-like structure in which residues P38 to P42 form a type II beta-turn conformation. An intermolecular antiparallel beta-sheet is formed between the peptide and the CDR3-H loop of the antibody; additional polar interactions occur between main-chain atoms of the peptide and hydroxyl groups from tyrosine residues protruding from CDR1-L and CDR3-H. Three water molecules, located at the antigen-antibody interface, mediate polar interactions between the peptide and the most buried hypervariable loops, CDR3-L and CDR1-H. A comparison between the free and complexed Fab fragments shows that significant conformational changes occur in the long hypervariable regions, CDR1-L and CDR3-H, upon binding the peptide. The conformation of the bound peptide, which shows no overall structural similarity to the corresponding segment in HIV-1 protease, suggests that F11.2.32 might inhibit proteolysis by distorting the native structure of the enzyme.

Amino Acid Sequence↗
PubMed1998

Conformational flexibility in a highly mobile protein loop of foot-and-mouth disease virus: distinct structural requirements for integrin and antibody binding.

The G-H loop of foot-and-mouth disease virus VP1 protein is a highly mobile peptide, that extends from the capsid surface and that in native virions is invisible by X-ray crystallography. In serotype C, this segment contains a hypervariable region with several continuous, overlapping, B-cell epitopes that embrace the conserved Arg-Gly-Asp (RGD) cell attachment motif. The solvent-exposed positioning of this peptide by selective insertion into different structural frameworks of E. coli beta-galactosidase, generates a spectrum of antigenic variants which react distinctively with a panel of anti-VP1 monoclonal antibodies and exhibit different efficiencies as cell ligands. The cell attachment efficiency is much less restricted by the different positioning of the viral segment at the insertion sites. A molecular model of an inserted stretch reveals a highest flexibility of the RGD tripeptide segment compared with the flanking sequences, that could allow a proper accommodation to integrin receptors even in poorly antigenic conformations. The non-converging structural requirements for RGD-mediated integrin binding and antibody recognition, explains the dynamism of the generation of neutralisation-resistant antigenic variants in the viral quasi-species, arising from a conformational space of integrin-binding competent peptides. This might be of special relevance for foot-and-moth disease virus evolution, since unlike in other picornaviruses, the cell binding motif and the major neutralising B-cell epitopes overlap in a solvent-exposed peptide accessible to the host immune system, in a virion lacking canyons and similar hiding structures.

Amino Acid Sequence↗
PubMed2000

Canonical antigen-binding loop structures in immunoglobulins: more structures, more canonical classes?

Grafting the antigen-binding loops onto a human antibody scaffold is a widely used technique to humanise murine antibodies. The success of this approach depends largely on the observation that the antigen-binding loops adopt only a limited number of canonical structures. Identification of the correct canonical structure is therefore essential. Algorithms that predict the main-chain conformation of the hypervariable loops using only the amino acid sequence often provide this information. Here, we describe new canonical loop conformations for the hypervariable regions H1 and H2 as found in single-domain antibody fragments of dromedaries or llama. Although the occurrence of these new loop conformations was not predicted by the algorithms used, it seems that they could occur in human or mouse antigen-binding loops. Their discovery indicates that the currently used set of canonical structures is incomplete and that the prediction algorithms should be extended to include these new structures.

Algorithms↗
PubMed2000

Identification of ENV determinants in V3 that influence the molecular anatomy of CCR5 utilization.

The V3 loop of the ENV glycoprotein exerts a dominant influence on the interaction of gp120 with coreceptors. Primary env genes cloned from sequential isolates from two seroconverters revealed Pro-->Ala conversion in the conserved GPG motif of the V3 crown in seven of 17 R5 ENV. ENV containing the GPG motif in the V3 crown had fusogenic activity with chimeric receptors containing either the N terminus or loops of CCR5, whereas those with the GAG variant utilized only the former. Site-directed mutagenesis of multiple primary and prototypic R5 env genes demonstrated that the GPG motif was necessary for dual utilization of the N terminus and body of CCR5 in both gain and loss-of-function experiments. All ENV containing the GPG V3 crown showed CCR5 binding in the presence of soluble CD4, whereas it was not detected with the GAG variants. Molecular dynamic simulations of a V3 peptide predicts that the Pro-->Ala substitution results in a conformational change with loss of the crown structure. These studies demonstrate that sequences in the third hypervariable region determine the specificity of coreceptor utilization for fusion, and that a conserved motif in the crown directly influences the molecular anatomy of the interaction between gp120 and CCR5.

Amino Acid Motifs↗
PubMed2001

The 1.55 A resolution structure of Nicotiana alata S(F11)-RNase associated with gametophytic self-incompatibility.

The crystal structure of Nicotiana alata (ornamental tobacco) S(F11)-RNase, an S-allelic glycoprotein associated with gametophytic self-incompatibility, was determined by X-ray diffraction at 1.55 A resolution. The protein has a tertiary structure typical of members of the RNase T(2) family as it consists of a variant of the (alpha+beta) fold and has eight helices and seven strands. A heptasaccharide moiety is also present, and amino acid residues that serve as the catalytic acid and base can be assigned to His32 and His91, respectively. Two "hypervariable" regions, known as HVa and HVb, are the proposed sites of S-allele discrimination during the self-incompatibility reaction, and in the S(F11)-RNase these are well separated from the active site. HVa and HVb are composed of a long, positively charged loop followed by a part of an alpha-helix and short, negatively charged alpha-helix, respectively. The S(F11)-RNase structure shows both regions are readily accessible to the solvent and hence could participate in the process of self/non-self discrimination between the S-RNase and an unknown pollen S-gene product(s) upon pollination.

Amino Acid Sequence↗
PubMed1994

Oligonucleotide probes for mutans streptococci.

Oligodeoxyribonucleotide probes complementary to hypervariable regions of the 16S ribosomal RNA were designed for specificity toward Streptococcus mutans and Streptococcus sobrinus. The probes were tested for specificity and sensitivity by hybridization with nucleic acid from over 100 mutans and non-mutans oral streptococci and other common oropharyngeal bacteria. Probes designated SM002 and SM010 were 100% sensitive and > 99% specific for S. mutans. Probe SSP001, designed to detect both S. mutans and S. sobrinus, was 88% sensitive and > 99% specific. The probes were able to detect nucleic acid extracted from 3 x 10(4)-1 x 10(5) homologous bacteria. Sensitivity did not vary significantly with the growth state of the cells, except for diminished signals when using nucleic acid extracted from very old cultures. The probes correctly identified 72 S. mutans colonies isolated from 10 volunteer saliva samples, using sugar utilization patterns as a reference standard. Ten isolates resembling S. mutans by colony morphology but not by sugar utilization patterns were correctly distinguished from mutans streptococci by the probes. These results demonstrate that oligonucleotide probes can accurately identify S. mutans in saliva samples.

Base Sequence↗
PubMed1997

The structure of human lupus anti-DNA antibodies.

B-cell hyperactivity and production of pathogenic autoantibodies are the main immunological events in the pathogenesis of the human autoimmune disease systemic lupus erythematosus. One approach to studying the pathogenesis of this disease and to understanding how the autoantibody response is initiated and sustained has been to analyze the variable genes expressed by antibodies that have the hallmarks of the disease-causing subset of pathogenic autoantibodies. Such studies have provided important clues. Quantitation of this repertoire revealed the presence of a specific expansion of IgG clonotypes that impart reactivity with disease-related autoantigens. The sequences of the genes encoding autoantibodies derived from these patients and expressing nephritogenic idiotopes (present in immune complexes and renal eluates of subjects with active disease) show features of molecular diversification with a high rate of replacement/silent mutations and clustering of the mutations in the hypervariable regions. These characteristics imply that a pure polyclonal B-cell activation process cannot be the only mechanism responsible for autoantibody production. More likely, an antigen drive plays a role in generation of pathogenic autoantibodies. Based on additional studies of their light chain variable region genes, we have offered a novel genetically based model whereby B cells secreting pathogenic lupus autoantibodies are blocked in their capacity to turn off their autoreactivity and to acquire a new specificity, a mechanism called receptor editing. Studies of the molecular events involved in this mechanism and of the clonal fates of B cells in vivo will be important for future research.

Amino Acids↗
PubMed1997

Investigating phylogenetic relationships within the Apicomplexa using sequence data: the search for homology.

Whether stated explicitly or not, all molecular studies that seek to infer "homologies" among sequences or that attempt to determine the "relatedness" of taxa based on sequence comparisons are evolutionary studies. The generation of a reliable evolutionary hypothesis based on molecular sequences is dependent almost exclusively on the ability to align sequences such that bases or amino acids in the same position of two sequences are positionally homologous (i.e., they share the same position in the gene under study). The selection of suitable gene targets (commonly 18S small subunit rRNA gene sequences in the Apicomplexa) and appropriate ingroup and outgroup taxa will affect the ability to align sequences unambiguously. Mathematically derived alignments based on local sequence similarity have been shown to be less reliable than alignments based on conserved secondary structures coupled with an analysis of compensatory base changes. Use of staggered sequence alignments through hypervariable regions of 18S small subunit rRNA gene sequences in which subsets of taxa are aligned independently may permit inclusion of more of the primary sequences with an associated increase in information content in the data set. The use of these highly variable regions is critical for determining the branching order of closely related terminal taxa in the phylum Apicomplexa.

Animals↗
PubMed1993

Evidence of natural recombination within the S1 gene of infectious bronchitis virus.

During an outbreak of severe respiratory disease, a field strain of infectious bronchitis virus (IBV), PP14, was isolated from a bird in a Texas flock that had been previously vaccinated with an attenuated Mass serotype virus. After cloning and sequencing the S1 gene from several IBV strains, it was found that the 5' end of the cDNA was 96% identical to the published sequences of Mass41 and 77% identical with Ark99. The following 402 bases which included the hypervariable regions (HVR) of the S1 gene were 94% homologous with Ark99 and only 69% with Mass41. In addition, the HVR in the 3' noncoding region of the genome, which is totally absent in Mass41, was 99% homologous with the Ark99 strain. This abrupt shift in identity of PP14 in the S1 strongly indicated that a recombination event had occurred about 98 bases from the beginning of the S1 gene between an Ark-like and a Mass-like virus. Downstream, 33 bases from the PP14 recombination junction, a second putative "cross-over" site was identified in the S1 of the SE17 strain where the 5'131 bases of the S1 gene of the Ark99 and SE17 were found to be 95% identical and the following 368 base sequence was only 78% homologous. In addition, a second shift in homology in the S1 of SE17 was identified between nucleotide 1112 and 1460 which shared 95% identity with Mass41. The putative recombination junctions which were downstream of the signal sequence and upstream of the S1 HVR may represent a "hot spot," but not an exclusive region, for exchanging genetic material between IBV strains. Genetic shifts are apparently not only common mechanisms for variation in nature, but vaccine strains may actually play a critical role in these events in the evolution of virulent strains of IBV.

Animals↗
PubMed1994

Evolution and selection of hepatitis C virus variants in patients with chronic hepatitis C.

It has been shown that hepatitis C virus (HCV) populations in vivo are composed of different but highly homologous HCV genomes (quasispecies) as shown in the hypervariable region (HVR) that exists in the N-terminal of the envelope 2 gene of HCV, and that the predominant sequence of the HVR of HCV genomes changes rapidly over time. To further investigate genetic backgrounds of the change in the HVR of HCV genomes, 45 plasma samples serially obtained from nine patients with chronic hepatitis C were studied using population-based analyses. Total RNA was recovered and the envelope gene containing the HVR was amplified by the reverse transcription and nested polymerase chain reaction. The amplified cDNA was examined by the single strand conformation polymorphism (SSCP) analysis. Furthermore, 43 HCV sequences, separated by the SSCP analysis from three patients were determined by the dideoxy chain termination method, and the phylogenetic analysis was performed using the neighbor joining method. The SSCP analysis demonstrated that HCV population within each individual were composed of 1 to 6 quasispecies. These quasispecies populations in vivo changed sequentially in eight of nine patients. Gradual selections of coexisting quasispecies were observed over 6- to 18-month periods in three patients, whereas complete replacements of previous quasispecies by new quasispecies were repeatedly observed over few-month intervals in five patients. The phylogenetic analysis on these quasispecies revealed the continuous accumulation of mutations in two patients and discontinuous appearance of evolutionarily distant quasispecies in one patient. These results indicate that HCV genomes in vivo form quasispecies populations, and that these quasispecies populations change during the natural course of chronic infection. Genetic mechanisms underlining the change of the HVR of HCV genome appear to be either continuous accumulation of mutations or selective overgrowth of preexisting minor variants from the large spectrum of quasispecies populations.

Aged↗
PubMed1994

Dual specificity of a monoclonal anti-idiotypic antibody for HIV-1 neutralizing monoclonals 110.3 and 110.4 as well as the V3 loop of gp120.

Monoclonal antibodies (MAbs) 110.3 and 110.4 bind an epitope at the tip of the third hypervariable region (V3) of the envelope protein gp120 of human immunodeficiency virus type 1 (HIV-1). These MAbs inhibit HIV-induced syncytium formation and neutralize cell-free virus infection. Anti-idiotypic MAb alpha-id8, generated against 110.3, was found to mimic the V3 loop of gp120, as demonstrated by competition ELISA and by the generation of anti-anti-idiotypic sera which bound gp120 and a peptide representing the tip of the V3 loop. Interestingly, alpha-id8 itself also reacted specifically with both gp120 and the V3 loop peptide. Thus, alpha-id8 both mimics and binds directly to the V3 loop, suggesting that the V3 loop of gp120 may associate with itself.

Amino Acid Sequence↗