Heavy Chain Sequencing Revealed Five Basic Varieties of Heavy Chains

For heavy-chain sequencing studies, myeloma proteins were reduced with mercaptoethanol and alkylated, and the heavy chains were separated by gel filtration in a denaturing solvent. When the amino acid sequences of several myeloma protein heavy chains were compared, a pattern similar to that of the light chains emerged. The amino-terminal part of the chain, consisting of 100-110 amino acids, showed great sequence variation among myeloma heavy chains and was therefore called the variable (V) region. The remaining part of the protein revealed five basic sequence patterns, corresponding to five different heavy-chain constant (C) regions 8, y, € and a). Each of these five different heavy chains is called an isotype. The length of the constant regions is approximately 330 amino acids for 8, y, and a, and 440 amino acids for ^ and e. The heavy chains of a given antibody molecule determine the class of that antibody: IgM(^), IgG(y), IgA(a), IgD(8), or IgE(€). Each class can have either k or X light chains. A single antibody molecule has two identical heavy chains and two identical light chains, H2L2, or a multiple (H2L2)„ of this basic four-chain structure (Table 4-1).

Minor differences in the amino acid sequences of the a and y heavy chains led to further classification of the heavy chains into subisotypes that determine the subclass of antibody molecules they constitute. In humans, there are two subisotypes of a heavy chains—a1 and a2—(and thus two subclasses, IgA1 and IgA2)—and four subisotypes of y heavy chains: y1, y2, y3, and y4 (therefore four subclasses, IgG1, IgG2, IgG3, and IgG4). In mice, there are four subisotypes, y1, y2a, y2b, and y3, and the corresponding subclasses.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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