Biomedical subjects

S R Zhou

Publications and source records attributed to S R Zhou.

At least 19 recordsLinked to original sources

PubMed1998

A cross-reactive anti-myelin basic protein idiotope in cerebrospinal fluid cells in multiple sclerosis.

We wanted to find evidence of antibody to myelin basic protein (MBP) in patients with MS by detecting their shared usage of immunoglobulin genes. As demonstrated by the idiotopes (i.d.) of murine monoclonal antibody to peptides of MBP, there is limited use of the variable (V) region immunoglobulin genes for the immune response in mice to this encephalitogenic protein. Cross-reactive Ids have been detected across different murine strains and shared by T and B cells. One cross-reactive Id, designated as 845D3 Id, is located on the V region of kappa light chains of two murine monoclonal antibodies, one to MBP peptide 80-89 and the other to MBP peptide acetyl 1-9. To examine the occurrence of 845D3 Id in MS, we used the V region of a light chain (VL) of one of the monoclonal antibodies to probe the VL genes expressed in B cells in CSF of 50 patients (31 MS and 19 non-MS). The VL genes expressed in B cells found in CSF were amplified by polymerase chain reaction using universal human V-region primers. The 845D3 Id probe detected the Id+ V region in the CSF of 14 of 31 MS patients, 1 of 9 patients with other neurologic diseases, and 1 of 10 non-neurologic patients. The gene product was more common in but not restricted to CSF with oligoclonal bands. The presence in CSF of MS patients of a cross-reactive Id to different MBP peptides is indicative of an immune response to this encephalitogenic myelin protein in a segment of MS patients. These findings are also evidence for limited usage of V-region Ig genes in the immune response of humans to MBP and the possible importance of an Id network for MBP in demyelinating disease.

Adult↗

PubMed1996

Active immunization with complementary peptide PBM 9-1: preliminary evidence that it modulates experimental allergic encephalomyelitis in PL/J mice and Lewis rats.

The idiotype (Id) of T cells and possibly antibodies are involved in an Id network that may immunoregulate experimental allergic encephalomyelitis (EAE). Thus, the adoptive EAE in PL/J mice responding to myelin basic protein (MBP) peptide acetyl 1-9 can be modulated by monoclonal antibody (mAb) anti-Id generated by immunization with a peptide of inverted hydropathy to MBP peptide 1-9, designated as PBM 9-1. A cross-reactive Id between species can be recognized on the T cell receptor (TCR) of Vb8.2 restricted T cells in either PL/J mice or Lewis rats. The present study was undertaken to examine the vaccine effect of PBM 9-1 presented in the form of a multiple antigen peptide (MAP) to induce active immunity against active EAE in Lewis rats and active or adoptive EAE in PL/J mice. MAP-PBM 9-1 induced an antibody response in both Lewis rats and PL/J mice, but more in the former. A low level of anti-Id antibody, including a low level of reactivity with specific but not control T cells, was also detected in the sera collected before induction of or after recovery from EAE. Active immunization with MAP-PBM 9-1 had a protective effect on relapses of adoptive EAE in PL/J mice and could prevent active EAE in Lewis rats. A relationship was noted between the titer of serum anti-PBM 9-1 Ab and the protective effect of active immunization in Lewis rats. Although the mechanism of effect remains to be clarified, these results suggest that MAP-PBM 9-1 is a nonencephalitogenic candidate for protection against inflammatory demyelination.

Amino Acid Sequence↗

PubMed1996

Murine V lambda x and V lambda x-containing antibodies bind human myelin basic protein.

Myelin basic protein (MBP) is highly immunogenic and a known autoantigen capable of inducing experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis. We have previously described a murine monoclonal antibody (mAb), F28C4, directed against the encephalitogenic MBP peptide acetyl (Ac) 1-9, which contains a V lambda x light chain. Considering the rarity of V lambda x usage, we determined whether other Abs having V lambda x light chains shared similar antigen (Ag) specificity. We screened a panel of V lambda x-containing monoclonal and polyclonal Abs, of unknown specificity for reactivity with MBP. All such Ab, but not heavy chain isotype matched controls, bound MBP but were not polyreactive with other potential self Ags. The binding of a recombinant form of V lambda x alone to MBP demonstrated the important contribution of the V lambda x light chain to the reaction. With the exception of mAb F28C4 which recognizes MBP Ac1-9, the epitope specificity of all other V lambda x-bearing Abs was localized to MBP residues 25-34. These results demonstrate a unique association between V lambda x expression and MBP reactivity. Given that V lambda x shares sequence homology with T cell receptors (TCR) from encephalitogenic T lymphocytes, these results imply a potential role for V lambda x in the pathogenesis of EAE.

Amino Acid Sequence↗

PubMed1996

Preferential association of V lambda x light chains with gamma 2a heavy chains in naturally occurring human myelin basic protein reactive antibodies.

Active immunization with myelin basic protein (MBP) induces experimental allergic encephalomyelitis (EAE) in a variety of animal species, including rats and mice. We have previously described the ability of the newly described mouse lambda (lambda) variable (V) region V lambda x, to confer MBP reactivity to an Ab. In this report, we have evaluated the heavy (H) chain isotype distribution of V lambda x-bearing Abs in normal mouse serum. We demonstrate a biased H chain isotype association with V lambda x light (L) chains with a skewing towards gamma 2a and 2b isotypes. The IgG2a restriction in normal mouse Igs is even more evident in V lambda x-containing Abs that bind MBP. This was confirmed by the ability of purified polyclonal IgG2a Abs to bind MBP and the finding that most or all of the IgG2a Abs that bind MBP seem to harbor a V lambda x L chain. The specificity of naturally-occurring V lambda x-bearing Abs with MBP can be localized to a particular epitope encompassing residues 25-34 of the MBP molecule. Furthermore, virtually all of the reactivity of V lambda x-containing Abs with MBP peptide 25-34 is associated with the gamma 2a isotype. Collectively, these results suggest that the interaction of V lambda x with MBP seems to be facilitated by an association with gamma 2a which may reflect preferred VH usage by this isotype. Such unique pairing of particular H chains with V lambda x L chains in Abs that bind MBP may be indicative of a new B-cell component involved in the pathogenesis of EAE.

Animals↗

PubMed1995

The effects of citrullination or variable amino-terminus acylation on the encephalitogenicity of human myelin basic protein in the PL/J mouse.

The post-translational modifications of myelin basic protein (MBP) in the form of citrullination and varying length of amino-terminus acylation may modify the biological functions and immunological features of MBP. Both modifications influence the reaction of antibodies and specific T cells recognizing MBP. The present study was undertaken to compare the encephalitogenicity of the citrullinated isomer of MBP (MBP-C8) with the unmodified isomer of MBP (MBP-C1) and to determine if the length of amino-terminal acylation of MBP peptide 1-21 altered an encephalitogenic epitope. MBP-C8, whether from patients with or without multiple sclerosis (MS), and MBP-C1 could induce active experimental allergic encephalomyelitis (EAE) in PL/J mice. A trend of reduced severity of EAE was observed in MBP-C8-injected animals. An increase in the length of amino-terminus fatty acid decreased the encephalitogenicity of MBP peptide 1-21 for both active and adoptive EAE in PL/J mice. Only lymph node cells sensitive to MBP peptide acetyl 1-21 and butyl 1-21 could transfer clinical EAE. In adoptive EAE, MBP peptides hexyl and octyl 1-21 induced moderate histopathological but no clinical change, whereas MBP peptide decyl 1-21 caused neither. A broadening in the antibody response could be detected in the sera of mice with active EAE induced by MBP-acylated peptides 1-21. Our findings demonstrate that encephalitogenicity is retained in the presence of citrullination but that the length of amino-terminus acylation diminishes the encephalitogenicity of MBP in the PL/J mouse.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗

PubMed1994

A cross-reactive idiotope on T cells from PL/J mice and Lewis rats that recognizes different myelin basic protein encephalitogenic epitopes but is restricted by TCR V beta 8.2.

Encephalitogenic T cells of both PL/J mice and Lewis rats are restricted by TCR V beta 8.2, although they recognize different epitopes in the myelin basic protein (MBP) molecule. We sought the presence of a cross-reactive idiotope (Id) in encephalitogenic T cells of Lewis rats by examining the effects of mAb F30 anti-Id, which recognized a TCR Id in PL/J T cells, on the encephalitogenic LR88L1 cell line derived from Lewis rats and specific for guinea pig MBP peptide 68-88. The LR88L1 cells were I-A restricted and TCR V beta 8.2+, and their proliferation and secretion of IL-2 and TNF-alpha induced by guinea pig MBP peptide 68-88 was inhibited by mAb F30 anti-Id. As shown by FACS analysis and by immunoprecipitation of TCR from radiolabeled LR88L1 cell lysates, the F30 anti-Id bound to the TCRs of V beta 8.2+ LR88L1 cells. In addition, TCR sequences in the F30+ population of LR88L1 cells were the same as those of encephalitogenic Lewis rat T cells published previously. The F30+ LR88L1 cells showed reduced encephalitogenicity compared with F30- or unsorted LR88L1 cells. The mechanism for this reduction by anti-Id probably resulted from the induction of anergy, in that IL-2 reversed the anti-Id effect. The control LR99L1 T cell line, also encephalitogenic, but specific for MBP peptide 87-99 and I-E, and not TCR V beta 8.2 restricted, failed to react with, or have its cytokine secretion inhibited by, mAb F30 anti-Id. These results demonstrate an interspecies cross-reactive Id expressed in common by encephalitogenic T cells that share a similar TCR, although they differ in MBP epitope specificity. These findings suggest that a common Id restricted by TCR, but less restricted by the encephalitogenic epitope, and recognized by the Id-bearing autoreactive T cells may represent an immunotherapeutic approach for treating autoimmune demyelinating diseases.

Amino Acid Sequence↗

PubMed1994

A V lambda x-bearing monoclonal antibody with similar specificity and sequence to encephalitogenic T cell receptors.

The fine specificity of mAb F28C4 to myelin basic protein (MBP), acetyl residues 1-9, has been compared with the previously described specificity of an encephalitogenic T cell clone, PJR-25. F28C4 has been found to express a cross-reactive idiotope (CRI) that is shared with MBP acetyl peptide 1-9-specific TCR. The CRI seems to be located at or near the Ag-combining site of F28C4 and the TCR and, thus, might possibly result from overlapping epitope specificity. We tested the fine epitope specificity of F28C4 by using alanine-substituted peptide analogues and found that residues critical for TCR recognition, Cln3 and Pro6, are also necessary for F28C4 recognition. By using nuclear magnetic resonance, we found that the MBP acetyl peptide 1-9 binds F28C4 in an extended conformation and that the central residues are more tightly bound than the terminal residues, much like the MBP-TCR interaction. Furthermore, sequence homology (75% overall) was found between the regions that contained CDR3 of F28C4 VL and VH and the VDJ junction of the TCR V beta. This homology is not shared by other Ig CDR3 regions and arises, in part, because F28C4 uses an unusual V lambda light chain, V lambda x. Thus, F28C4 shares a CRI with the TCRs, possibly as a result of having similar fine epitope specificity and sequence homology. The anti-CRI mAb can down-modulate experimental allergic encephalomyelitis; thus, it is possible that Abs that are similar to F28C4 may play an important immunoregulatory role in experimental allergic encephalomyelitis in vivo.

Amino Acid Sequence↗

PubMed1994

Comparison of properties of murine monoclonal anti-idiotypic antibodies generated with idiotype-bearing monoclonal antibodies to myelin basic protein peptides or their complementary peptides.

The present study was undertaken to compare the features of monoclonal antibody (mAb) anti-idiotope (Id) induced by complementary peptides, synthesized on the basis of inverted hydropathy for a myelin basic protein (MBP) peptide, or by conventional methodology using Id-bearing antibodies to the same MBP peptide as immunogen. The six reagents studied consisted of mAbs reactive with MBP peptide acetyl 1-9 and MBP peptide 80-89 and anti-Id reagents against these two mAbs prepared by either the complementary peptide or the conventional approach. ELISA, immunoblotting, immunoinhibition of hybridoma cell production of Id-bearing mAb to MBP, and FACS indicated that the anti-Ids generated by either technique were similar although existing in a range reflecting biologic phenomena. mAbs anti-Id prepared by either method continued to show an IgM isotype preference, possibly related to technical considerations, and continued to recognize a cross-reactive Id on the kappa light chain of the mAbs to MBP peptides acetyl 1-9 and 80-89. There was no indication that the anti-Ids prepared by the complementary peptide approach were restrictive or selective in a manner different from those made by the conventional approach.

Amino Acid Sequence↗

PubMed1994

Identification of interactive determinants on idiotypic-anti-idiotypic antibodies through comparison of their hydropathic profiles.

We have written a computer program to aid in the identification of interaction sites between proteins. The program compares the hydropathic profiles of the two interacting proteins and reports sites, demonstrating an exact pattern of inverted hydropathy. If these regions are surface accessible in the folded proteins, they are considered putative binding or docking sites and can be tested as such. In this report, we apply this program to the localization of residues involved in the anti-idiotope of a monoclonal antibody (mAb), F30C7. The anti-idiotope of F30C7 partially resembles the structure of the peptide antigen, human myelin basic protein (MBP) acetyl 1-9, used to elicit the idiotope bearing mAbs (Ab1). The sequences of F30C7 variable regions are compared to the variable regions of Ab1, as well as to the peptide antigen used to elicit F30C7. Sites of hydropathic complementarity in F30C7 with Ab1 that also have sequential homology with MBP 1-9 were located, and a synthetic peptide designed from these sequences was found to structurally resemble MBP 1-9 in that it: (i) inhibited Ab1 binding to MBP 1-9 and (ii) partially inhibited the binding of F30C7 to Ab1. Thus the portion of the anti-idiotope of F30C7 resembling MBP 1-9 was determined with the aid of this program. Other hits between F30C7 and Ab1 also occurred, and future studies will determine whether or not these sites might further contribute to the anti-idiotope.

Amino Acid Sequence↗

PubMed1994

Use of complementary peptides and their antibodies in T-cell-mediated autoimmune disease: experiments with myelin basic protein.

In this article we review the field of idiotype (Id) network and experimental allergic encephalomyelitis, focusing on the generation of monoclonal antibody anti-Id by using complementary peptide and the investigation of anti-Id immunoregulatory effects on immune responses of B and T cells to specific myelin basic protein peptides in vitro and in vivo.

Amino Acid Sequence↗

PubMed1994

Monoclonal antibodies to a TCR idiotope modulate the superantigen-induced responses of encephalitogenic rat T cells.

Superantigens, such as staphylococcal enterotoxins, activate T lymphocytes by linking MHC class II molecules on antigen presenting cells to the V beta element of the TCR. Through this effect on T cells, superantigens may influence the immune response and autoimmune disease. In fact, superantigens may activate or anergize cells involved in the production of experimental allergic encephalomyelitis. Lewis rats recognize an encephalitogenic epitope in myelin basic protein (MBP) residues 68-88 through an MHC class II I-A restricted process using TCR V beta 8.2. The F30 murine mAb reacts with an encephalitogenic idiotope (Id) on the TCR of V beta 8.2+ encephalitogenic Lewis rat T cells. In the present study it was demonstrated that the same mAb anti-Id inhibited the proliferation and IL-2 secretion induced by staphylococcal enterotoxins A, B and E in a V beta 8.2+ encephalitogenic Lewis rat T cell line specific for guinea pig MBP peptide 68-88. The mAb anti-Id did not inhibit the response of control T cells similarly derived but inhibited V beta 8.2- and recognizing MBP peptide 87-99. Control anti-Id failed to inhibit the response of either cell line. These findings imply that the specific antigen and superantigen react with TCR in a manner similar enough to be inhibited by the same anti-Id. The mechanism may involve the induction of anergy by the anti-Id, interference/steric hindrance by the reaction of anti-Id with TCR and possibly a little direct reaction of anti-Id with superantigens. Anti-Id directed immunotherapy may have a role in modulating the damage of inflammatory demyelination induced by both specific antigens and superantigens.

Amino Acid Sequence↗

PubMed1993

Specific modulation of T cells and murine experimental allergic encephalomyelitis by monoclonal anti-idiotypic antibodies.

Acetylated peptide 1-9 from human myelin basic protein induces experimental allergic encephalomyelitis in PL/J mice through I-Au and TCR V beta 8.2. Murine mAb anti-Id directed against murine mAb to myelin basic protein peptide acetyl 1-9 was examined for effects on in vitro and in vivo T cell activities. Certain anti-Id, generated in PL/J mice, inhibited Ag-specific proliferation and IL-2 production and precipitated surface receptors having features of the TCR. The idiotypic features of TCR recognition were demonstrated by showing that binding of anti-Id to the TCR could be blocked by anti-TCR alpha beta and anti-TCR V beta 8.1-8.2 but not by murine Ig or anti-TCR V beta 17a. In addition, the anti-Id did not react with TCR V beta 8.2 transgenically inserted into MRL+/+ mice. One anti-Id was also capable of lessening clinical disease activity in the adoptive passive transfer model of experimental allergic encephalomyelitis in PL/J mice. These results indicate that anti-Id may recognize a cross-reactive Id on T cells, presumably on the TCR, responsive to the same I-Au-restricted encephalitogenic myelin basic protein peptide in PL/J mice. The selective development of anti-Id and their effect on T cell-mediated tissue damage provide a method for applying specific anti-Id antibodies to modify experimental and, possibly, spontaneous diseases of autoimmune demyelination.

Amino Acid Sequence↗

PubMed1993

Immunological analysis of the amino terminal and the C8 isomer of human myelin basic protein.

The citrullination and N-terminus acylation of myelin basic protein (MBP) increases the heterogeneity among the MBP isoforms. The present study was undertaken to further characterize the immune response to the citrullinated form (C8) of MBP as well as to the variably acylated N-terminus of MBP. Six well-characterized murine monoclonal antibodies (mAbs) to human MBP-C8 or MBP peptides (four mAbs to MBP acetyl 1-9, one mAb to MBP 10-19 and one mAb to MBP 80-89), one murine T cell line (PL11) to human MBP peptide acetyl 1-9 and one Lewis rat T cell line (RT-1) to guinea pig (GP) MBP peptide 68-88 were used to assess reactivity with MBP-C1, MBP-C8, and MBP peptides including a series of MBP peptide 1-21 containing 0, 2, 4, 6, 8 or 10 carbon fatty acids. Enzyme-linked immunosorbent assay (ELISA) results revealed that all of the mAbs reacted with human MBP-C1 and MBP-C8 except anti-MBP 10-19 and anti-MBP-C8. The former reacted only with MBP-C1 and the latter only with MBP-C8. The presence and length of acylation of MBP peptide 1-21 modified reactivity. Three mAbs to MBP acetyl 1-9 reacted only with acetyl 1-21, and one mAb anti-MBP actyl 1-9 reacted with all of MBP 1-21 preparations whether acylated or not. mAb anti-MBP-C8 generally reacted better with acylated MBP 1-21 having longer fatty acids. The PL11 T cell line strongly proliferated to human MBP-C1, MBP-C8 and MBP acetyl 1-9, responded, but less well, to MBP 1-21 with longer fatty acids and failed to respond to nonacylated MBP peptide 1-21. The RT-1 cell line responded strongly to GP MBP peptide 68-88, marginally to MBP-C8 and failed to respond to MBP-C1 or any of the other MBP peptides. Specific immune responses to different MBP charge isomers and different N-terminal acylating groups of MBP may play a role in immune-mediated demyelination.

Acylation↗

PubMed1993

The structure of a myelin basic protein-associated idiotope.

A cross-reactive idiotope (CRI) has been previously described on monoclonal antibodies (mAbs) specific for encephalitogenic peptides from myelin basic protein (MBP). The anti-CRI mAb, F25F7, binds an idiotope (Id) localized to the light chains of an anti-MBP peptide 1-9 mAb, denoted F23C6, and an anti-MBP peptide 80-89 mAb, denoted 845D3. It is the purpose of this study to further delineate the CRI being recognized by F25F7. To this end, we have found a structural correlation between the CRI and the antigen, a small synthetic peptide, denoted PBM 9-1, used to elicit the anti-Id mAb. Sequence comparison between the light chain of F23C6 and PBM 9-1 reveals a region of homology in CDR 2/FWK 3. The configuration of this site in the VL, as determined by comparison with a mAb, HyHEL-10, whose structure has been determined and is 97% homologous to the light chain of F23C6, conforms to the rules used to define antigenic determinants or Ids. A synthetic peptide having the F23C6 VL CDR 2/FWK 3 sequence inhibited the binding of F25F7 to F23C6 and 845D3. Taken together, these data suggest the Id recognized by F25F7 is defined, in part, by the PBM 9-1-like sequence of F23C6.

Amino Acid Sequence↗

PubMed1992

Interstrain cross-reactive idiotypes on monoclonal antibodies to an encephalitogenic myelin basic protein peptide.

In order to assess the role of idiotype (Id) and the anti-Id network in murine experimental autoimmune encephalomyelitis (EAE), Id-bearing monoclonal antibodies (mAb) to human myelin basic protein (MBP) peptide acetyl 1-9, as well as mAb anti-Id, were developed in EAE-susceptible PL/J mice (H-2u). These mice recognize MBP residues acetyl 1-9 as an encephalitogenic determinant. Reactivities of PL/J Id-bearing mAbs to MBP and to MBP peptides were identical to those of mAbs generated against the same MBP peptide in EAE-resistant BALB/c mice (H-2d), even though isotypes of the mAbs differed. By using an inhibitory ELISA and immunoblotting, it was demonstrated that one PL/J mAb anti-Id recognized a public or framework Id, whereas another PL/J mAb-anti Id was directed to a private Id more restricted to the paratopic site. Two Id-bearing PL/J mAbs shared a cross-reactive Id (IdX) on the light chain, and an interstrain IdX was present on both the heavy and light chains of mAbs raised in PL/J and BALB/c mice to the same MBP peptide. The PL/J mAb anti-Id was capable of cross-regulating the production of Id-bearing mAbs by hybridomas across murine strains. These findings suggest that a restrictive family of germ-line genes encode for these Id-bearing antibodies to MBP peptide, irrespective of whether the MBP peptide is encephalitogenic in the murine strain immunized. Manipulation of the Id network may provide a means for modifying autoimmune demyelinating diseases of the central nervous system.

Animals↗

PubMed1992

An immunochemical comparison of human myelin basic protein and its modified, citrullinated form, C8.

An immunochemical analysis was conducted to compare the C1 isomer of human myelin basic protein (MBP) with the newly described and less cationic, citrullinated isomer of MBP referred to as C8. Ten polyclonal antisera directed at multiple epitopes or restricted regions of MBP were used in radioimmunoassays to examine MBP-C1 and MBP-C8. Antisera reactive with MBP peptide 1-14 clearly distinguished MBP-C1 from MBP-C8. Antisera to human MBP peptides 10-19 and 90-170, but not to MBP peptide 69-89, showed modest differences between MBP-C1 and MBP-C8. The MBP-C8s from multiple sclerosis (MS) and non-MS brain reacted essentially the same. With murine monoclonal antibodies and enzyme-linked immunosorbent assay (ELISA), differences between MBP-C8 and other isomers were shown for anti-MBP 10-19 but not for anti-MBP 1-9 or anti-MBP 80-89. These findings imply differences in sequence or conformation in the structure of MBP-C7 compared to MBP-C1, most notably near the amino terminus.

Adult↗

PubMed1991

Changes induced in astrocyte cathepsin D by cytokines and leupeptin.

Cathepsin D is widely, but unevenly, distributed among cells and is capable of degrading a number of neural peptides and proteins. The present study was undertaken to examine the level of cathepsin D in astrocytes that might be relevant to its induction in inflammatory demyelination. Primary astrocytes were cultured from neonatal rat cerebrums according to the method of McCarthy and de Vellis. Based on staining for cell markers, cultures were greater than 95% astrocytes and less than 3% microglia. Under serum-free conditions, leupeptin induced a 1.4- to 2.0-fold increase, maximal by 48 hours, in cathepsin D protein quantified by a radioimmunoassay. Cathepsin D enzymatic activity, inhibitable by pepstatin, also increased. Northern blot analysis demonstrated that leupeptin also increased cathepsin D mRNA expression. Kinetic analysis indicated that maximal cathepsin D mRNA levels are detected 24 h after stimulation with leupeptin. Exposure of astrocytes under the same conditions to rat recombinant interferon-gamma, human recombinant tumor necrosis factor-alpha, human recombinant interleukin-1 beta, lipopolysaccharide, calcium ionophore, or a combination of these reagents did not increase the level of cathepsin D above controls. These results indicate that astrocytic cathepsin D mRNA and protein can be induced by selected materials. Furthermore, the effects attributed to leupeptin as a proteinase inhibitor may be modified by its ability to increase cathepsin D activity.

Analysis of Variance↗

PubMed1990

An idiotype shared by monoclonal antibodies to different peptides of human myelin basic protein.

A mAb of the IgG1/kappa isotype was raised against human myelin basic protein (MBP) peptide acetyl 1-9. This mAb, termed F23, reacted with human MBP and human MBP peptides acetyl 1-9, 1-14, and 1-44, but not with MBP peptides 10-19, 80-89, or 45-89. According to the guidelines of the molecular recognition theory, a complementary peptide to human MBP peptide 1-9 was synthesized and used to raise murine mAb with anti-Id activity. Two mAb anti-Id, F25F7 and F25C8, both of the IgM/kappa isotype, were selected for further study. These anti-Id reacted with F23, the mAb for which they were selected, and also reacted with another mAb, which was of the IgG1/kappa isotype and was raised to human MBP peptide 80-89. There was no reaction with another control mAb of the IgG1/kappa isotype or murine myeloma IgG1. By immunoblotting techniques, it was demonstrated that the Id on each of the mAbs to MBP peptides was located on the kappa L chain but also could be recognized in nonreduced IgG. The cross-reactive anti-Id suppressed antibody secretion of Id-producing hybridoma cells in an Id-specific manner, and kinetic studies suggest an intracellular mechanism for the suppression. These cross-reactive Id among antibodies to different MBP peptides imply that the same V region genes of kappa L chains are involved in the selection of antibodies to an autoantigen, like MBP, and may play a role in the modulation of immune responses against MBP in certain inflammatory demyelinating diseases.

Amino Acid Sequence↗