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H G KUNKEL

Publications and source records attributed to H G KUNKEL.

At least 19 recordsLinked to original sources
PubMed1965

INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS. CHARACTERISTICS AND LOCALIZATION TO SUBUNITS.

The specific antigenic structure of individual myeloma proteins was investigated for the presence of similar antigenic determinants in pooled gamma-globulin and for the localization of these determinants on the gamma-globulin molecules. Quantitative precipitin analyses demonstrated that in most instances absorption of antisera specific for an individual myeloma protein with large amounts of gamma-globulin markedly reduced or completely removed the reactivity of the antiserum for the homologous myeloma protein. In only one instance did strong specificity remain after absorption with 100 mg of Fr II per cc of antiserum. The antigenic determinants responsible for the individual specificity were localized in all cases studied solely to the Fab fragment produced by papain digestion. After reductive cleavage, three patterns of localization were observed. Individual specificity could be localized either to; (a) isolated heavy chains, (b) isolated light chains, (c) antigenic determinants present only when light and heavy chains were recombined. After immunization with whole myeloma proteins, individual specificity was localized in part at least to the isolated heavy chain in four of six proteins studied. It was localized to the light chains in three of five type L proteins but in none of six type K proteins. In the instances where individual specificity of the myeloma protein was present on the light chains, it was shown that the Bence Jones protein from the same patient also contained the individual specificity. Immunization with isolated heavy or light chains furnished further evidence for the individual specificity of both types of chains. These studies on myeloma proteins furnished evidence concerning the portions of the gamma-globulin molecule subject to individual antigenic variation. The light chains, particularly the L type and the Fd portion of the heavy chains were primarily involved. Evidence for the importance of the quaternary structure was also obtained from the necessity in some instances for light and heavy chains to be associated in order for individual specificity to be observed. The Fc fragment of the heavy chains on the other hand showed very limited variation which was related to subgroup specificity.

Antigens↗
PubMed1964

ACTIVITY OF DISSOCIATED AND REASSOCIATED 19S ANTI-GAMMA-GLOBULINS.

19S anti-gamma-globulins were isolated in a high state of purity from the sera of two patients with rheumatoid arthritis. Following reduction with ethyl mercaptan and alkylation by iodoacetamide, fragments were produced which retained the capacity to combine with 7S gamma-globulin. The fragments from one of the 19S anti-gamma-globulins agglutinated red cells coated with incomplete anti-Rh antibodies. This activity was shown by density gradient ultracentrifugation to be associated with low molecular weight fractions. The agglutination of the coated red cells by the fragments was strongly inhibited by normal and myeloma 7S gamma-globulins and showed a greater specificity than the parent 19S material. Analytical ultracentrifuge experiments demonstrated that the fragments from either of the 19S anti-gamma-globulins formed complexes with 7S gamma-globulin. Reassociation of the dissociated fragments through reformation of disulfide bonds resulted in the formation of fast sedimenting molecules having properties similar to those of the untreated 19S material in respect to precipitation with aggregated gamma-globulin and agglutination of coated red cells.

Antibodies, Anti-Idiotypic↗
PubMed1964

H CHAIN SUBGROUPS OF MYELOMA PROTEINS AND NORMAL 7S GAMMA-GLOBULIN.

Through the use of a variety of antisera to isolated myeloma proteins, four subgroups of 7S gamma-globulin type proteins were readily distinguished. The first, the Vi subgroup, consisted of ten of 64 myeloma proteins studied. The second, the We group, contained the majority of myeloma proteins. The third, the Ge subgroup, included three of 50 myeloma proteins. The fourth remains ill-defined and appears heterogeneous. Counterparts for both the Vi and the Ge subgroup, were found in the Fr II gamma-globulin and in the normal gamma-globulin of all of a large number of individual sera studied. The unique antigenic character of both groups was localized to the H chains, although different determinants were involved for different antisera. An essential role of intact disulfide bonds was apparent with certain rabbit antisera. In addition to the special antigenic characteristics, the Ge subgroup showed in each instance a fast mobility for the F fragments produced by papain which was not found for other myeloma proteins.

Antigen-Antibody Reactions↗
PubMed1964

STUDIES ON HUMAN ANTIBODIES. II. DISTRIBUTION OF GENETIC FACTORS.

Human antibodies against dextran, teichoic acid, blood group A substance, levan, tetanus toxoid, and nuclei were isolated and analyzed for their content of Gm(a), Gm(b), and Inv(a) gamma-globulin genetic factors. The majority of these antibodies contained all the genetic factors determined in the donor's whole gamma-globulin, but in many antibodies at very different concentrations. In a few instances specific factors could not be detected despite their presence in the individual's whole gamma-globulin. Different antibodies isolated from the serum of the same individual showed different relative concentrations of genetic factors. The distribution of genetic factors seen in certain isolated human antibodies appeared to approach the selective occurrence of these factors in myeloma proteins.

ABO Blood-Group System↗
PubMed1963

LOCALIZATION OF ANTIBODIES IN GROUP I AND GROUP II GAMMA-GLOBULINS.

A wide assortment of antibodies has been analysed by qualitative and quantitative techniques for their content of group I- and group II-type gamma-globulin molecules. These included Rh antibodies, isoagglutinins, thyroglobulin antibodies, dextran antibodies, and teichoic acid antibodies. All the antibodies studied showed the presence of both groups. However, the ratio of the two varied widely in different individuals and diverged markedly from the ratio in the total gamma-globulin of the individual. Two antibodies isolated from the serum of the same individual showed different ratios for the two groups.

Antibodies↗
PubMed1963

Antibodies to genetic types of gamma globulin after multiple transfusions.

Seventeen of 24 sera from children who had received multiple transfusions contained agglutinating antibodies against a Gm factor absent in the individual's serum gamma globulin. Each of these agglutinators was highly specific for a single Gm factor, and all proved useful as reagents for genetic typing. The accumulated evidence indicates that they resulted from genetically foreign gamma globulin introduced by transfusion.

Antibodies↗
PubMed1962

Genetic characters of human gamma-globulins in myeloma proteins.

The genetic factors Gm(a), Gm(b), Gm(x), and Inv(a), Inv(b) described for normal human gamma-globulin were all found in different myeloma proteins. A single myeloma protein never contained more than one product of alternate alleles even in heterozygous individuals. However, factors determined by the two different loci were often found in the same myeloma protein. The Gm(a) character of the myeloma protein parallelled that of the normal gamma-globulin of the same serum in most cases. In contrast, the Gm(b) character was usually absent in the myeloma protein when it was directly demonstrable in the normal gamma-globulin. The myeloma proteins from six Negroes were Gm(a+b-), whereas the normal gamma-globulin was Gm(a+b+). This indicates that the effect of gene Gm(b) is similar in Negroes and whites, even though its relation to gene Gm(a) is different in the two races. Gm factors were found only in the 7S gamma-globulin type myelomas and not in other products of plasma cell tumors. Inv characters were, however, present in all four types of proteins studied, namely 7S and 19S gamma-globulins, beta(2A)-globulins, and Bence Jones proteins. In two instances, genetic heterogeneity of the protein products was demonstrated suggesting the proliferation of more than one clone of plasma cells in some multiple myeloma patients. The accumulated evidence obtained in this study strongly suggested that the presence and absence of genetic characters was compatible with the concept that myeloma proteins were closely analogous to individual moieties in the spectrum of normal gamma-globulins rather than truly abnormal proteins. Their study offered evidence of a heterogeneity of genetic characters among the normal gamma-globulins in a given individual. It also appears probable that in normal individuals single plasma cells have a restricted capacity to express genetic information in their protein product.

Bence Jones Protein↗
PubMed1962

Localization of two genetic factors to different areas of gamma-globulin molecules.

Gm(a) and Gm(b) factors are present in 7S gamma-globulin molecules and absent in 19S gamma-globulins, beta(2A)-globulins and Bence-Jones proteins, whereas the Inv(b) factor was demonstrated in all four kinds of proteins. The Inv type was identical in isolated 7S and 19S gamma-globulins of six normal sera. After papain splitting of 7S gamma-globulin, Gm determining sites were present only in the fast (F) split product and Inv determining sites were present only in the slow (S).

Bence Jones Protein↗