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J M Kehoe

Publications and source records attributed to J M Kehoe.

At least 37 records · Page 2Linked to original sources
PubMed1974

Structure of antibodies with shared idiotypy: the complete sequence of the heavy chain variable regions of two immunoglobulin M anti-gamma globulins.

The complete amino acid sequence of the heavy chain variable regions of two different molecules of immunoglobulin M anti-gamma globulin has been determined. These proteins, from different human patients, had independently been shown to share idiotypic specificity. Only eight sequence differences were discernible for the entire length of their heavy chain variable regions. Five of the differences occurred outside hypervariable regions, while three were placeable within such regions. A comparison of these molecules of anti-gamma globulin with the seven human V(H)III variable region sequences presently available for immunoglobulins without known antibody activity showed that the great majority of sequence differences between the two idiotypically similar antibodies and these seven proteins were confined to hypervariable regions. This study illustrates in precise terms a convergence of the distinct immunological properties of idiotypy, hypervariable region structure, and combining site specificity as they relate to the variable region of the immunoglobulin molecule. To a great degree these properties now appear to be a reflection of the same structural attributes of the variable region.

Amino Acid Sequence↗
PubMed1974

Variable region sequences of five human immunoglobulin heavy chains of the VH3 subgroup: definitive identification of four heavy chain hypervariable regions.

The variable regions of five human immunoglobulin heavy chains of the V(H)III subgroup have been totally sequenced. Three of the heavy chains belonged to the IgG class and two to the IgA class. Examination of these sequences, and comparison with additional published heavy chain sequences, showed that a total of four hypervariable regions is characteristic of human heavy chain variable regions. The relatively conserved character of large segments of the heavy chain variable region was very evident in these studies. The conserved segments, which are those sections located outside the hypervariable regions, comprise approximately 65% of the total heavy chain variable region. The following general structural pattern for antibody molecules emerges from this and related studies: an overall combining region superstructure is provided by the more conserved segments while the refinements of the active site specificity are a function of hypervariable regions.

Amino Acid Sequence↗
PubMed1973

Phylogenetically associated residues within the VH3 subgroup of several mammalian species. Evidence for a "pauci-gene" basis for antibody diversity.

Immunoglobulin heavy chains from IgG pools of several mammalian species have been subjected to Edman degradation on an automated protein sequencer. The percentage of unblocked vs. blocked heavy chains was estimated from the yield of the invariant valine in the second position. Further analysis of these unblocked polypeptides unequivocally placed them in the V(HIII) subgroup on the basis of homology with known human heavy chain sequences. The mammals studied could be divided into three distinct categories on the basis of the distribution of the V(HIII) subgroup. In several species the V(HIII) subgroup could not be detected while, in others, virtually all of the heavy chains belonged to this subgroup. Several species had intermediate amounts with the level of the V(HIII) subgroup restricted to between 19 and 29% of the total pool. Within experimental error, all members of a given order had a similar V(HIII) subgroup distribution. Further amino acid sequence studies illustrated a high degree of structural homogeneity in the heavy chains of IgG isolated from pooled sera of a number of mammalian species. The very close amino acid sequence homologies of the amino terminal 24 residues of the various pools corroborated conclusions previously obtained using several myeloma proteins from some of these same species. In particular, certain phylogenetically associated residues were identifiable at characteristic positions in the pools in confirmation of their identification in the myeloma proteins. The simplest assumptions would suggest that these findings are more compatible with a pauci-gene than a multi-gene basis for the generation of antibody diversity.

Amino Acid Sequence↗
PubMed1972

Light chain sequences of human IgM cold agglutinins (variable-region subgroups amino-acid sequence-kappa light chain-N-terminal).

The amino-terminal amino-acid sequence has been determined for the kappa light chains of nine IgM cold agglutinins with specificity for blood group-related carbohydrate antigens. Six of the nine sequences corresponded to the prototype VK(III) subgroup pattern, two to that of subgroup VK(II), and only one to the VK(I) subgroup. This distribution of kappa subgroups differs markedly from that of normal and myeloma proteins sequenced to date, where the VK(I) subgroup is more prevalent than either VK(II) or VK(III). Evidence is presented that supports the conclusion that the unusual subgroup distribution relates to the antibody property itself and not to some other attribute of these molecules.

Amino Acid Sequence↗
PubMed1972

Evolution of neurophysin proteins: the partial sequence of bovine neurophysin-I (vasopressin-oxytocin-carrier proteins-automated amino-acid-sequence analysis-homology-protein evolution).

The sequence of the first 50 amino-acid residues of bovine neurophysin-I was determined. A comparison of this sequence with that of the 97-residue bovine neurophysin-II and the 92-residue porcine neurophysin-I molecules reveals a high degree of homology among these proteins. It is suggested that the binding site of neurophysin proteins for neurohypophyseal hormones is located in the middle portion of these molecules, where their sequences are virtually identical. The sequence data, as well as the occurrence of at least two neurophysins in both the pig and the cow, suggest that each species inherited at least two structural genes controlling the synthesis of these proteins. The most striking finding in the study was the observation of internal sequence homologies within the neurophysins. This result implies that these molecules arose by way of a series of partial gene duplications of a primitive gene that coded for a smaller ancestral protein.

Acetamides↗
PubMed1972

Sequence relationships among the variable regions of immunoglobulin heavy chains from various mammalian species.

Immunoglobulin heavy chains of myeloma proteins from dogs and cata have been subjected to automated sequence analysis. When the results were compared with human heavy-chain sequences, all the dog and cat proteins could be unequivocally assigned to the V(H)III subgroup. This pattern contrasts with that in human proteins in which only 25% of all heavy chains sequenced belong to this subgroup. The 30 residues at the NH(2) termini of dog, cat, and human heavy chains had sequence identities near or exceeding 90%, in contrast to established interspecies sequence homologies of constant regions of about 60%. Some genes of the immunoglobulin heavy-chain variable region thus appear to have been conserved through a considerable period of evolutionary time. The analyses also showed that the presence of certain amino acids at certain positions in these heavy chains could be correlated with the species of origin. The occurrence of such "phylogenetically associated" residues is most consistent with the presence of a restricted number of genes in the heavy-chain variable region pool.

Amino Acid Sequence↗
PubMed1971

Localization of two additional hypervariable regions in immunoglobulin heavy chains.

Cyanogen bromide fragments were isolated from the heavy chains of three human IgG myeloma proteins of the V(H)III subgroup, sequenced by an automated method, and localized to the variable region. Inspection of these sequences, together with corresponding stretches from both human and animal proteins (studied in other laboratories) led to the detection of two additional hypervariable regions characteristic of the V(H) segment of immunoglobulin heavy chains. These areas of hypervariability, involving heavy-chain residues 86-91 and 101-109, were separated by a region of relative constancy. The close relationship of these two hypervariable regions, and the previously described first heavy-chain hypervariable region (residues 31-37), to the first heavy-chain disulphide bridge implies that the three hypervariable areas might be in close steric approximation in native immunoglobulin molecules. Examination of the sequences of the terminal portion of V(H) of all these proteins (the segment from residue 95 to the beginning of homology region C(H)l) revealed that no subgroup-specific residues could be identified in this area. Thus, heavy-chain subgroup distinctions may not extend through the entire variable region.

Amino Acid Sequence↗