Page 499 - Veterinary Immunology, 10th Edition

Cattle
VetBooks.ir Cattle are the only mammals known to possess two functional

heavy chain loci. Most of these genes are located on chromosome

21, but a truncated µCH2 exon is present on chromosome 11. The
genes on chromosome 21 are organized thus: (n denotes a variable
number of these genes, p denotes a pseudogene).
5'-Vn-Dn-Jn-M1- (D1p-V3-D1n) -Jn-M2-D-G3-G1-G2-E-A-3'.
3
Thus there are internal duplications of DH, JH, and C region
genes. Both IgM genes can be expressed independently or

sequentially by class switching. Cattle have three IGHG genes
corresponding to their three subclasses: IgG1, IgG2, and IgG3. IgG1
constitutes about 50% of the serum IgG and is the predominant
immunoglobulin in cows' milk rather than IgA. IgG2 levels are
highly heritable and its concentrations vary greatly among cattle.

Cattle possess a unique Fc receptor on their macrophages and
neutrophils that binds only IgG2. Since bovine IgG2 has a very
small hinge region, this receptor might represent a special

adaptation to the structure of this immunoglobulin.
Some cattle immunoglobulin molecules are unusually large
because they use a long third hypervariable polypeptide loop
(CDR3) that may contain up to 69 amino acids. This length is due to
a very long germline Dh2 gene segment that encodes four cysteines

that form interchain bonds with each other, together with repeated
glycine, serine, and tyrosine residues. As a result, these heavy chain
CDR3s fold into a long stalk supporting a disulfide-bonded “knob”

domain located far from the antibody surface (Figs. 16.16 and
16.17). The knob folds into a mixture of minidomains generated by
multiple mutations involving cysteine residues. It is this protruding
knob and stalk that recognizes antigens. The benefits of this
structure are unclear.

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