Subunits of immunoglobulins and their relationship to antibody specificity.
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Biomedical subjects
Publications and source records attributed to R R Porter.
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The heavy chain of a pathological human immunoglobulin IgG and also the Fd fragment have been isolated. No free alpha-amino group was present on either and the N-terminal sequence of both has been identified as pyrrolid-2-one-5-carbonylvalylthreonine. Splitting at the four methionine residues of the heavy chain with cyanogen bromide gave five fractions. The fraction from the C-terminal end of the chain was isolated in high yield and the amino acid sequence was: His-Glu-Ala-Leu-His-Asp(NH(2))-His-Tyr-Thr-Glu(NH(2))-Lys-Ser-Leu-Ser-Leu-Ser-Pro-Gly These results give strong support to the view that the heavy chain of immunoglobulin is a single peptide chain.
A study of the chemical structure of the horse immunoglobulins IgG and IgA(T) has shown that the amino acid contents of the peptide chains are very similar. These globulins differ most markedly in the products of papain digestion. IgG gives 3.5s products, whereas IgA(T) gives a 5s fraction and smaller components. This difference appears to be associated with the presence of an additional easily reducible disulphide bond in the Fd fragment of the heavy chain. There is two to three times as much carbohydrate in IgA(T) as in IgG. In both, this is in the heavy chain and in IgA(T) more than half is covalently bound to the Fd fragment. The differences in antigenic specificity between horse IgG and IgA(T) appear to be due to structural differences in the Fc fragment.
The antigen-binding capacity of the peptide chains of horse anti-(diphtheria toxin) has been studied by using (125)I-labelled toxoid and electrophoresis of antibody-antigen mixtures on cellulose acetate. The heavy chains retained about 20% of the activity of the whole antibody and the light chains less than 5%. Recombination of specific heavy and light chains gave about 60% recovery of activity and recombination of specific heavy chains and non-specific light chains about 40% recovery. It is suggested that these results favour the heavy chain as the major site of the antigen-binding activity.
The absence of an N-terminal amino acid with a free alpha-amino group from the heavy chain of rabbit immunoglobulin IgG has been confirmed and no evidence could be found of a blocking formyl, acetyl or propionyl group. The N-terminal amino acid appears to be pyrrolid-2-one-5-carboxylic acid (PCA) in all molecules. A mixed amino acid sequence follows in the approximate proportions: PCA-Ser-Val-Glu-Glu-Ser-Gly-Gly-Arg, 50%; PCA-Ser-Leu-Glu, 20%; PCA-Glu(NH(2)), 20%. The heavy chains of a purified antibody, namely anti-(human serum albumin), and of immunoglobulin IgG from a rabbit homozygous at the allotypic loci both showed a similar mixed N-terminal sequence.
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Genes coding for the complement proteins C2, C4A, C4B and factor B lie between HLA-D and HLA-B in HLA, the major histocompatibility complex in man. All the complement components are polymorphic, particularly C4, which has many alleles at each locus. The genetic complexity of C4 extends to the number of loci each of which may be deleted or duplicated on the chromosome. The different forms of C4 showed markedly different reactivities with small molecules and on haemolytic activity in the complement system. Surprisingly, amino acid sequences of the several allelic forms of C4 appear to be very similar, with less than 1% of residue positions being changed between alleles of C4A and C4B. These results may be relevant to the increased susceptibility to autoimmune disease which is associated with particular haplotypes of the HLA complex.
Four human complement genes, which have previously been mapped between HLA-D and HLA-B on chromosome 6, have now been aligned on a 98-kilobase (kb) section of the chromosome on the basis of four overlapping cosmid clones of genomic DNA. The C2 and factor B genes, less than 2 kb apart, are about 30 kb from two C4 genes separated from each other by about 10 kb.
The effectiveness of the transplantation team in diffusing stress during the pretransplantation period is increasingly important the longer the patient remains on the transplant waiting list. This study describes the stressors and coping strategies of heart transplant candidates during the waiting period. Thirty-nine candidates on the active list for heart transplantation from four mid-East Coast transplantation centers participated. With a possible stress score of 0 to 243, the mean score for this sample was a low 72.84 (standard deviation = 37.47). The three most common stressors were (1) requiring a heart transplant, (2) having terminal heart disease, and (3) worrying family members. The three most common coping strategies were (1) thinking positively, (2) using humor, and (3) trying to keep life as normal as possible. The finding of low stress levels was surprising but may reflect the presence of hope or the patient's desire to spare family members worry--a concern commonly cited by patients. Another explanation is that patients desiring to be perceived as ideal transplant recipients may have underreported their stress. This suggests that the transplantation team should support positive coping strategies when possible and that both patient and family coping should be closely monitored throughout the waiting period.