Immunoglobulins allotypes, human

W.H.O. Review of the notation for the allotypic and related markers of human immunoglobulins. W.H.O. Meeting on Human Immunoglobulin Allotypic Markers. (1976) J. Immunogenet. 3. 

Antigenic markers (allotypes) of immunoglobulin molecules were almost simultaneously reported for human and rabbit antibodies. Oudin (1956) observed that rabbit antibodies themselves elicited precipitating antibodies when they were injected into certain other rabbits. Oudin named the phenomenon allotypy and the antigenic determinants on the immunoglobulin molecules were called allotypes. At the same... 

The differences in the titer of antiallotype antibody produced reflect the particular antigenic determinants involved. The allotypic determinants of human immunoglobulins are small, often single amino acid interchanges in proteins of the same subclass. Amino acids involved in the determinant may be considerably removed from one another in the linear sequence in those instances when more than one amino acid is important, however. Examples are the group a and b allotypic determinants of rabbits which involve multiple amino acid differences scattered along the chain (Kindt, 1975). 

Allotypic markers have been found on H chains of human IgG, IgM, and IgA and on k chains, but not as yet on the H chains of IgD or IgE or in human X chains. In each instance, antiserum has been used for the initial classification, but more recent studies have related a number of allotypic variations to differences in amino acid sequence. With one probable exception, allotypic differences attributable to carbohydrate have not been reported. All allotypic markers so far identified in human immunoglobulins are present in Ch and Cl regions. 

Thus considerable progress has been made in identifying, characterizing, and locating the antigenic determinants associated with a number of human allotypic markers. These determinants are often quite complex with contributions from amino acids that are widely removed from one another in the linear sequence. This is therefore still another area where the details of the tertiary, or quaternary, structure of the immunoglobulin are crucial to the expression of a given function. 

In this chapter we will discuss amino acid sequences of human and mouse L chains and of human and rabbit H chains. A few sequences of rabbit L chains are also tabulated. Other partial amino acid sequences are presented in connection with the phylogeny of immunoglobulins (Chapter 7), and allotype-related sequences are discussed in Chapter 9. The amino acid sequences to be discussed here represent only a small fraction of the existing literature but should serve to illustrate principles of immunoglobulin structure. 

In this chapter we shall describe properties of immunoglobulins of four mammalian species that have been studied quite extensively the rabbit, mouse, guinea pig, and horse. Human inununoglobulins are considered in Chapter 3 and the pattern of evolution of immunoglobulins in vertebrates in Chapter 7. Allotypy of immunoglobulins is reviewed in Chapter 9 and will not be considered here. Because of the extensive body of information available on amino acid sequences and allotypes a more complete understanding of the structure of the immunoglobulins of these species will require reference to Chapters 4 and 9. 

In most, but not all immunoglobulins, one disulflde bond joins an H chain to an L chain. There are marked variations, however, with respect to H-H disulflde bonds. The number of such bonds, where known, is indicated by the diagrams in Table 8.1. An unusual chain structure, analogous to that found in the Azmll) allotype of human IgA2 (14,15) is observed in the IgA of BALB/c (16,16a,17) but not NZB mice (18) the L chains are disulflde bonded to one another, as are the H chains, but there are no H-L disulflde bonds. The H and L chains are therefore separable in the presence of a a dissociating agent such as 1 M acetic acid, without prior reduction of disulflde bonds. 

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