Heavy chain of immunoglobulin

Porter, R.R., The structure of the heavy chain of immunoglobulin and its relevance to the nature of the antibody-combining site the Second CIBA Medal Lecture. Biochem 1,1967.105(2) 417-26. 

Gm and Inv are amino acid sequences occurring in the light and heavy chains of immunoglobulins (16, 18). Antibodies specific to the Gm and Inv groups are found in some patients suffering from rheumatoid arthritis and in some healthy people. 

The existence of such variation in the N-terminal half of the light chains while the C-terminal half remained constant was a new phenomenon in protein chemistry. As the number of sequences increased and as such data on mouse Bence Jones proteins and later on heavy chains of immunoglobulins were accumulated, it became clear that understanding the nature of the structural and genetic basis for the variable domains of both chains was crucial to understanding antibody specificity. 

A cyclic, internal amide derivative of glutamic acid is pyrrolidone carboxylic acid (also known as pyroglu-tamic acid or 2-oxoproline). Some proteins (e.g., heavy chains of immunoglobulins Chapter 35) and peptides (e.g., thyrotropin-releasing hormone Chapter 33) have py-roglutamic acid as their N-terminal amino acid residue. 

Another type of regulation of processing involves choice of different sites of polyadenylation. One example is the differential synthesis of the hormone calcitonin in different tissues another is the synthesis of two forms of the heavy chain of immunoglobulins (Chapter 35). In both cases, the differential processing includes distinct patterns of intron excision (i.e., splicing), but they are necessitated by an earlier event in which differential poly(A) sites are selected from the primary transcript. That is, when the poly(A) site nearer the promoter is selected, a splice site used in the larger primary transcript is not present, so a different splice pattern results. Thus, slightly different proteins are synthesized. 

Protein Fv was isolated and purified by Jean-Pierre Bouvet et al. [1] in 1990 from stool extracts obtained from 43% of patients affected by viral hepatitis C (HCV) and from 35% of patients with hepatitis B (HBV). This factor (originally called protein F ) was found in only 6.7% of healthy subjects. The original name soon became protein Fv (for Fv fragment) because Bouvet and Pillot [2] provided evidence that this factor binds to the variable domain of the heavy chain of immunoglobulins. Molecular sieving by high performance liquid chromatography of protein Fv indicated an apparent molecular... 

It seems clear that the existence of distinct isotypic determinants is due to specific conformational features of the constant region of the heavy chains of immunoglobulins. Unlike for some other protein systems, however, such as myoglobin (Atassi, 1975) and lysozyme (Atassi et al., 1976 Lee and Atassi, 1977a,b Atassi and Lee, 1978a,fo Atassi, 1978), the location of the various determinants has not been precisely mapped and correlated with particular structural features. 

Fig. 4. Enzyme inhibition Effect of an epitope specific antibody. Various amount of C-1-23 antibodies were incubated for 4 hr at 4°C with 500 ng of enzyme and subsequently assayed using standard conditions (6) for 5 min at 30° C in presence of 10 pg of DNA and total histone and 200 pM [ P-]N (30,000 cpm/nmol). The percentage of inhibition is defined as (1 minus the ratio of the activity in the presence absence of antibodies) x 100. The specific activity of the purified enzyme after a 4 hr incubation was 1150 nmol/mg/ min. Gel analysis of the mixture of an enzyme to antibody weight ratio of 1 is shown before (0) and after (4) incubation. E enzyme, Lc light c n and He heavy chain of immunoglobulin.

D-Mannose and 2-amino-2-deoxy-D-glucose residues become attached to nascent heavy chains of immunoglobulins soon after the site for glycosylation is biosynthesized and therefore prior to the completion of translation. After completion of the polypeptide chain and its release from the ribosome, sequential addition of residues of 2-amino-2-deoxy-D-glucose and D-galactose... 

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