Mouse allotypes

Allotypy has been studied most extensively in the rabbit, man, and mouse. In each species allotypic variation is seen in both H and L chains. In the rabbit and in man, for which data are available, genes controlling allotypic determinants on H and L chains are unlinked. In the mouse, allotypic variability of L chains has been detected by peptide mapping but, so far, not through antigenic analysis. 

Early investigations of mouse allotypes were reported by Kelus and Moor-Jankowski (193), by Dubiski and Cinader (194), and by Lieberman and Dray (195). Much of the more recent work discussed here has been carried out in the laboratories of M. Potter, R. Lieberman, and L. Herzenberg. 

The mouse allotypes are often referred to by the inbred strain in which they occur. For example, the complete allotype (G , A ", p8,i9 of... 

Structural correlates for mouse allotypes have not yet been described, but the recent completion of the amino acid sequence of a mouse IgG H chain indicates that such data will be available in the near future. 

Fab (50 kd) and scFv (27 kd) antibody fragments have shorter plasma half-lives (0.5 to 21 hours) because of more rapid glomerular filtration and clearance [7], Plasma clearance, particularly of the xenogenic (usually mouse) portions of humanized and/or chimeric monoclonal antibodies, might be accelerated by development of anti-mouse (or other species), anti-isotypic, anti-idiotypic, or anti-allotypic antibodies that foster immune complex formation or reticuloendothelial clearance via several different FcR forms or elicit allergic or anaphylactic responses [7,8]. 

High variability was noted also at positions 81, 83, 84, 85 when human heavy chains were examined, and this is considered another hypervariable region by Capra and Kehoe (1974). Unlike the other hypervariable regions it became less marked when several species of heavy chain were considered. It is not seen in mouse heavy chains (Vrana et al., 1977) and is not apparent when all heavy-chain data are combined (Fig. 6). Residues 84 and 85 of rabbit heavy chains, however, are involved in a allotypic specificity (Ansari et al., 1976 Mage,... 

Ropkov M., Jendreyko N., Gonzalez-Sapienza G., Mage R. G., Rader C., and Barbas C. F. 3rd. Human/mouse cross-reactive anti-VEGF receptor 2 recombinant antibodies selected from an immune b9 allotype rabbit antibody library, J. Immunol. Methods., 288(1-2), 149-164, 2004. 

By far the greatest number of different allotypic markers have been found in man. Allotypes have also been found in a number of other species, however, including the rabbit, mouse, rat, cow, and chicken. For this chapter, we will be concerned mainly with structural correlates of human and rabbit allotypes. The general subject of allotypes is extremely well described in several excellent reviews (Mage et aL, 1973 Natvig and Kunkel, 1973 Kindt, 1975 Kunkel and Kindt, 1975), and the reader is directed to these for additional information. 

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. 

Fig. 4.1. Complete amino acid sequences of human and mouse k and X chains. For simplicity the Roy (V, ) numbering system is used. The gaps, i.e. at position 27, are required to accomodate the sequences. References used are human k, Roy (4) human X, Bo (151) mouse k, M41 (152) and mouse X, 104E (55). See footnote 1 for description of the conventions used. Allotypic substitutions are shown at position 191 of the human k chain, and isotypic substitutions at positions 143, 152,172, and 190 of the human X chain. In Fig. 4.3, which considers only X chains, the numbering system of human X protein New is employed. This changes the position numbers of the isotypic substitutions at positions 143 and 152 to 144 and 153, respectively.

The additional presence of 4.5 M urea is required for mouse IgA or IgG (3a). In the IgA of BALB/c mice and in human IgA2 of allotype Ajm( I) L chains are not disulfide bonded to the H chains. These exceptions are discussed in Chapters 8 and 3, respectively. 

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. 

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