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PubMed1974

Partial amino acid sequence in the N-terminal region of an anti-pneumococcal immunoglobulin heavy chain of allotype alpha2.

The amino acid sequence of the N-terminal 48 residues of the heavy chain derived from a homogeneous rabbit antibody to type III pneumococci is described. This chain of allotype a(2) is compared with other rabbit heavy chains of allotypes a(1), a(2) and a(3). Within the N-terminal 25 positions, two chains which carry the same allotype a(2) possess identical amino acid sequences, but differ markedly from heavy chains of allotypes a(1) and a(3). Sequence variability is observed in residues 26-27 and 30-34, but not in residues 35-48.

Amino Acid Sequence↗
PubMed1983

Rabbit immunoglobulin kappa genes: structure of a germline b4 allotype J-C locus and evidence for several b4-related sequences in the rabbit genome.

To investigate the genetic mechanism by which certain rabbits can express immunoglobulins unexpected on the basis of their pedigree (i.e., "latent" allotypes), we have begun a study of the rabbit immunoglobulin kappa gene locus. Here we report the structure of a germline genomic clone that encodes the b4 allotype of rabbit kappa immunoglobulin and corresponds to the kappa gene expressed by the rabbit-mouse hybridoma 12F2. The nucleotide sequences of the joining (J) and constant (C) regions reveal structures generally similar to the homologous mouse and human loci, although only one of the five J-like sequences of this rabbit gene is apparently expressed. Southern blotting analysis of DNA from several rabbit allotypic strains by using probes derived from the cloned b4 gene demonstrates that, in contrast to mouse and human, rabbits possess multiple kappa-related sequences. Rabbits of the nominal b4, b5, b6, and b9 allotypes each contain at least two b4-related sequences that are associated with their own J regions and that are highly homologous to the cloned b4 gene in both coding and flanking regions.

Animals↗
PubMed1984

Induction of immunoglobulin allotypic suppression in the rabbit: a cellular approach.

Adult rabbits were sensitized against rabbit immunoglobulin allotypic specificities of the a and b series by means of two injections of their own lymphocytes coated with the appropriate IgG. The splenic lymphocytes from these sensitized rabbits were injected, 24 hr after birth, into newborns that had inherited from their father the allotypic specificities susceptible to recognition by the sensitized lymphocytes. A significant percentage (40%) of the young rabbits subjected to this treatment developed a total suppression of expression of these specificities with the well-known compensatory effect due to an increased expression of the corresponding allele. We have observed that the T Julius subset of the sensitized splenic lymphocytes was responsible for the induction of this suppression that was established without discernible intervention of anti-allotype antibodies. In one instance we observed that the expression of the allotypic specificities transmitted by the father, although established at 5 weeks of age, gradually declined and totally disappeared at 13 weeks of age.

Animals↗
PubMed1977

The inheritance of antibody V regions in the rabbit: linkage of an H-chain-specific idiotype to immunoglobulin allotypes.

Anti-idiotype antibodies specific for the H chain of an homogeneous antistreptococcal antibody (4135 Ab) were prepared by injection of recombinant molecules consisting of the H chains from 4135 Ab and L chains isolated from the injected rabbit. The antibodies prepared in this fashion (anti-HId) were specific for the VH region of 4135 Ab. Using this preparation in an inhibition of binding assay, sera from rabbits related and unrelated to 4135 were screened for the presence of the 4135 HId. It was found that about 45% of the related rabbits, when immunized with streptococcal Group C vaccine, produced antibodies with a cross-reactive idiotype, while less than 10% of similarly immunized unrelated rabbits produced molecules bearing HId. The expression of HId was linked to the a3 allotype present in the H chain allogroup J. Antibody molecules bearing the HId determinant were isolated from heterozygous (a1a3 and a2a3) rabbits and shown to express the a3 allotype. One rabbit lacking the a3 allotype produced significant amounts of antibodies expressing HId. These antibodies were found to express both VH and CH allo-types characteristic of the J allogroup, although neither allotype was found in a preimmune IgG sample from this rabbit.

Animals↗
PubMed1978

The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody.

The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder x high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.

Animals↗
PubMed1979

A role for clonal dominance in the maintenance of allotype suppression?

The establishment of immunological memory during the early and complete phase of allotype suppression in the young rabbit has been shown to lead to the preferential production of antibodies with the nonsuppressed allotypic specificity in response to recall injections given after spontaneous or induced release from suppression. It is suggested that this manifestation of clonal dominance, applied to stimulation by environmental antigens, may contribute to the long lasting persistence of allotype imbalance in allotype suppressed rabbits.

Animals↗
PubMed1982

Two distinct allotypic determinants on the antigen-specific suppressor and enhancing T cell factors that are encoded by genes linked to the immunoglobulin heavy chain locus.

The alloantiserum was raised in BALB/c (H-2d, Igh-1a) mice hyperimmunized with spleen cells of Igh allotype congenic mice, CB-20 (H-2d, Igh-1b). It was found to define the new allotypic determinants (distinct from B cell Igh constant region determinants: Igh allotype) expressed only on a small population of T cells belonging to the Thy-1 dull-stained Lyt-2- or Lyt-2+ population of Igh-1b mice. Genes coding for the determinants were shown to be accommodated somewhere in the right side of the Igh variable region gene (Igh-V) cluster, as the antibody activity was completely absorbed with BAB-14 thymocytes. It was also demonstrated that the products detected by the antiserum represent the allotypic determinants (probably constant region determinants) on the antigen-binding moiety of the antigen-specific augmenting (TaF) and suppressor (TsF) T cell factors. Moreover, determinants on TsF were found to be distinct from those on TaF. Therefore, it can be suggested that the two genes coding for the T cell allodeterminants (distinct from those of the B cell Igh) are located in the right side of the B cell Igh-V on the 12th chromosome, and that both encode the antigen-recognition units of the functionally distinct T cell factors.

Animals↗
PubMed1979

Gm and Km allotypes in disputed parentage.

Immunoglobulin allotyping in 925 cases of disputed paternity provided evidence of exclusion for 70 alleged fathers. Combining results from erythrocytic antigen, enzyme, and serum protein tests, 230 men were proven to be falsely accused; in 15 cases the immunoglobulin allotype provided the only evidence for exclusion, in 67 no exclusion would have been identified if testing had been limited to ABO, Rh, and MNSs. Various cases in this study illustrate the importance of using an extensive battery of immunoglobulin reagents in order maximally to exclude falsely accused men, and to identify infrequent haplotypes, which might erroneously be interpreted as indirect exclusions or may indicate a high likelihood of paternity. The problems of Gm typing of very young children are described. When child is less than 6 months of age, direct exclusions may be missed by the Gm allotypes; indirect exclusions are valid only when the phenotype differs from that of the mother. Km allotypes are not age-dependent.

Adult↗
PubMed1986

Antibody responses to Haemophilus influenzae type b polysaccharide vaccine in relation to Km(1) and G2m(23) immunoglobulin allotypes.

The antibody responses of children immunized with Haemophilus influenzae type b polysaccharide vaccine were examined in relation to the absence or presence of the Km(1) or G2m(23) immunoglobulin allotype. Ninety-seven children, 12-83 months of age, were immunized. Sera were obtained before immunization and two months later. Total serum antibody to the type b capsule was detected by a radioactive antigen-binding assay. IgG and IgM antibody responses were measured by enzyme-linked immunosorbent assay. Antibody responses to the type b capsule were more than threefold higher in blacks with the Km(1) immunoglobulin allotype compared with those in blacks lacking this allotype (P less than .02). The isotype affected was IgG (P less than .01) and not IgM. Serum concentrations of IgG2, but not of IgG1, also were higher in blacks with Km(1) (P less than .003). In whites there were no significant differences in the total or IgG-specific antibody responses to the type b capsule in relation to the Km(1) or G2m(23) allotype.

Antibodies, Bacterial↗
PubMed1984

Human immunoglobulin heavy chain A2 gene allotype determination by restriction fragment length polymorphism.

The human immunoglobulin heavy chain alpha 2 genes have two allelic forms or allotypes called A2m(1) and A2m(2). Previously, these allotypic markers have only been distinguishable by serology. Studies of the alpha 2 genes, however, show that it is possible to differentiate between the allotypes by restriction enzyme site polymorphisms, both in the protein coding regions and in flanking regions. These polymorphic sites have been used to determine the alpha 2 allotypes of several human DNAs.

Alleles↗
PubMed1978

Antagonism between donor and host B cells in allotype congenic chicken chimeras.

B cell chimerism was analyzed in juvenile chickens given injections of major histocompatibility complex-compatible lymphoid cells. The allelic products of donor and host-derived B cells were monitored with antisera directed against M1 (IgM) and G1 (IgG) isotype-specific allotypes. Injection of peripheral blood lymphocytes and spleen cells suppressed host allotype levels whereas purified T lymphocytes were ineffective. Pretreatment of recipients with cyclophosphamide was more effective than irradiation in promoting both engraftment and host B cell suppression. Host allotype suppression endured for several months after cell transfer and was attributable to B cell deletion, as ascertained by the lack of cells which expressed surface M1. In partially suppressed chickens, host G1 was inhibited to a greater degree than M1 allotype. Host recovery was followed by donor B cell rejection when low numbers of donor cells and/or inadequate host conditioning was used. Selective M1 chimerism occurred when limiting numbers of spleen cells were transferred into cyclophosphamide-treated hosts, whereas selective G1 chimerism resulted after the transfer of large numbers of peripheral blood lymphocytes or spleen cells into unconditioned recipients. We consider that these findings can be attributed to a B cell surveillance mechanism which may be similar to that postulated previously to explain resistance to haemopoietic and tumour cells.

Animals↗
PubMed1990

Evaluation of monoclonal antibodies with putative specificity for human IgG allotypes.

Fourteen monoclonal antibodies (MAbs) of putative specificity for human IgG allotypes and isoallotypes were evaluated for reactivity and specificity in 8 different assay systems. The study showed that the MAbs tested could be classified into 1 of 4 groups: those exhibiting allotypic specificity regardless of the assay system, allotypic specificity dependent on the assay system, isoallotypic specificity, and those showing neither allotypic nor isoallotypic specificity. These observations were presumably dependent on antigen presentation, epitope integrity and/or antibody multispecificity. For the G1m(a), G1m(f), G1m(z), G3m(g) and G3m(u) specificities, MAbs have been produced which can be used for routine typing purposes in defined haemagglutination and enzyme-linked immunosorbent assay systems. MAbs are also available that show 'non-g' isoallotypic specificity.

Animals↗
PubMed1997

The effect of race, smoking and immunoglobulin allotypes on IgG subclass concentrations.

In previous studies we have demonstrated that serum IgG subclass concentrations are influenced by both race and periodontal disease diagnosis. Furthermore, we have shown that smoking habits modify the concentrations of some IgG subclasses in specific racial and diagnostic groups. In view of a large amount of data showing strong associations between immunoglobulin allotypes and IgG subclass concentrations we have investigated the effects of race, smoking and IgG allotype on IgG subclass concentration in a population of subjects with or without various forms of periodontitis. The results indicated that there are complex relationships between these factors in their effects on individual IgG subclass levels, and that effects unique to black or white subject groups, or to specific periodontal diagnostic groups and racial subgroups, were evident. In blacks with chronic adult periodontitis IgG1 was lower in smokers, while in generalized early-onset periodontitis patients IgG2 was lower in smokers. IgG4 was independently affected by gender (males higher), smoking (smokers lower) and GM23 (GM23 positive subjects higher), in black subjects only. In white subjects, complex relationships between smoking and allotypic markers were noted but no influence of periodontal diagnosis was found. White GM23 negative subjects who smoked had lower levels of IgG1 than GM23 positive subjects. White GM2 negative subjects who smoked had lower levels of IgG2, than did those who did not smoke. In contrast, smoking had no effect on IgG2 levels in GM2 positive subjects. Thus, in addition to immunoglobulin allotype, smoking is associated with IgG subclass concentrations; furthermore, in black subjects, periodontal diagnosis, gender and smoking all influence IgG subclass concentrations. These results demonstrate that genetic and environmental factors can interact to influence levels of individual subclasses.

Adult↗
PubMed1983

Latent immunoglobulin G (Gm) allotypes: occurrence in the cerebrospinal fluid in some neuropathological states.

Gm allotypes were detected and quantitated by radioimmunoassay (RIA) in paired serum and CSF samples from patients suffering from various neurological diseases. Of 115 patients with neurological disorders (65 MS and 50 others), seven subjects displayed one or two allotypes in their CSF which were absent in serum. The Gm phenotype in the patient's serum allowed us to infer the genotype without the need of familial data. A comparison of the regression curves obtained in RIA from the unexpected allotype in CSF and the counterpart in a normal serum pool argued for an identity of the Gm antigen carried by both inhibitory molecules. The unexpected allotype(s) in CSF can be considered as the product of a latent Gm gene which may be activated by either immune perturbations due to the disease per se or some particular immune regulations in the central nervous system.

Humans↗
PubMed1996

IgE allotypes in sera of mice with autoimmune diseases and in mice with graft-versus-host disease after transfusion or bone marrow transplantation.

Isotype- and allotype-specific IgE determinations by sandwich ELISA with monoclonal antibodies to Igh-7 (6HD5, HMK-12), Igh-7a (No. 297) and Igh-7b /JKS-6) were used to qualitate antibodies of the IgE class. The sensitivity of the method is 0.1 ng/ml. Serum IgE levels were much higher in mice infected with Nippostrongylus brasiliensis. In sera of BALB/c, AKR and C3H/JCL mice only IgEa, in sera of C57BL/6 and CB-20 only IgEb, in sera of (BALB/c x C57BL/6) F1 mice, both allotypes were detected, as expected. In mice with autoimmune diseases, such as NZB, NZW, (NZB x NZW) F1, MRL/Ipr and MRL/n strains which all belong to the IgEa allotype group, IgE and IgEa were very high. In the sera of BXSB mice, both IgEa and IgEb were detected. Both IgEa and IgEb from donor and host were increased in the sera of mice with graft-versus-host disease after transplantation but only the IgEa (from the donor) was increased in mice with graft-versus-host disease after bone marrow transplantation. In the former, both B cells (from donor and host) secreted IgE, whereas in the latter only the donor cells did. These are the first observations showing the importance of IgE allotype secretion as an indication of graf-versus-host disease.

Animals↗
PubMed1985

Relation of age, race, and allotype to immunoglobulin subclass concentrations.

Concentrations of IgG1, IgG2, and total IgG were measured by a solid phase radioimmunoassay in sera from 36 healthy adults and 114 healthy children. As expected, IgG2 and total IgG had a positive correlation with age in children. In addition to age, several other factors were associated with significant differences in serum subclass concentrations. Female children had higher concentrations of IgG1 than males, and black subjects had significantly higher concentrations of IgG1, IgG2, and total IgG than whites. Although Km(1) and Gm(23) immunoglobulin allotypes had no relation to subclass concentrations when tested as single factors, the Km(1) allotype interacted significantly with race so that Km(1)-positive black children had higher IgG2 concentrations than other subjects. Our findings may explain, in part, recent observations of an association of the Km(1) allotype with altered immune responses of blacks to certain vaccines containing bacterial polysaccharides. In addition, our data indicate the need to control factors such as sex, race, and allotype in studies of subclass concentrations or immune responses.

Adolescent↗
PubMedDate not supplied

Expression of latent allotypes in SJL mice.

SJL mice (CH allogroup Igb) were immunized against immunoglobulins from strain BALB/c (allogroup Iga). We used either animals purchased directly from the Jackson Institute, or Jackson-derived mice which had been inbred further in our laboratory. In some mice from three independent immunization series we observed, contrary to expectation, the expression of molecules carrying allotypic determinants of Iga instead of the expected production of antibodies against these determinants. Various types of breeding experiments were carried out with parents being either "orthodox" SJL mice, or animals expressing the "wrong" allotype. Among the progeny, as analyzed so far, we again found animals which changed their allotype after antiallotypic immunization. The data do not appear to be compatible with a single-gene, dominant mendelian inheritance of allotypic determinants in this stock of mice.

Alleles↗
PubMed1976

Synthesis of Gm allotypes by human tonsillar lymphocytes in culture: concordance with serum phenotype.

Isolated human tonsillar lymphocytes were cultured with pokeweed mitogen, phytohemagglutinin, and without mitogen for 9 to 28 days. IgK, Gm(a) and Gm(f) were then quantitated in the cell suspensions. In cultures of cells derived from persons whose blood was heterozygous for IgGl allotype antigens Gm(a+f+), approximately equal amounts of Gm(a) and Gm(f) were found. In cultures of cells of Gma or Gmf homozygotes, there was complete concordance between the Gm allotype antigens produced by the cultures and the donor's serum phenotype-with no instance, either at zero time or at culture termination in which a Gm antigen was detected which was absent from the donor's serum. It was concluded that in vitro genetic allotype synthesis in tonsillar lymphocytes during short-term culture mirrored accurately in vivo Gm expression. IgK and Gm antigen synthesis was highest in the flasks containing pokeweed mitogen although both phytohemagglutinin and no-mitogen control flasks showed, in certain experiments, proliferation and an increase in the Ig per viable cell. It was observed that no-mitogen flasks contained twice as much allotype antigen as did phytohemagglutinin flasks suggesting an inhibition of Ig synthesis associated with the mitogen. The tonsillar lymphocytes, under the experimental conditions employed, were shown by a radio-incorporation and immunoprecipitation technique to be synthesizing polyclonal Ig de novo, at the termination of the cultures.

Cells, Cultured↗