Page 310 - Veterinary Immunology, 10th Edition

Mammals use two distinct strategies for maintaining high levels
VetBooks.ir of MHC class I diversity. Mice and humans simply use a small

number of highly polymorphic genes. In other primates, herbivores,
and rats, however, MHC diversity is generated by varying the

number and combinations of their class I gene loci.

Nonpolymorphic MHC Class I Molecules

Mammalian cells also express many nonpolymorphic class I

molecules. Some are encoded by genes within the MHC class I
region, others by genes on other chromosomes. They are classified
according to their evolutionary origin.
Class Ib molecules show reduced expression and tissue
distribution compared with class Ia molecules but are part of the

MHC complex. They have limited polymorphism and their genes
probably originated from class Ia precursors by duplication. For
example, the class Ib genes in mice are found in three loci called Q,

T, and M. They code for proteins on the surface of regulatory and
immature lymphocytes and on hematopoietic cells. These also
consist of a membrane-bound α chain associated with β -
2
microglobulin, so their overall shape and antigen-binding groove
are similar to those in MHC class Ia molecules. Since they are not
polymorphic, however, MHC class Ib molecules bind a limited
range of ligands. They act as pattern recognition receptors for

commonly encountered, microbial PAMPs.
Class Ic genes have limited polymorphism and are found within
the MHC. Their products include MIC-A and MIC-B, specialized
proteins that are involved in signaling to natural killer (NK) cells,

but do not bind antigenic peptides (Chapter 19).
Class Id genes are nonpolymorphic class I-related genes not
located on the MHC chromosome. Many of their products
contribute to innate immunity since they bind PAMPs. For

example, CD1 molecules are antigen-presenting receptors that bind
lipid antigens (Chapter 19). FcRn is a class Id MHC molecule that
acts as an antibody (Fc) receptor on epithelial cells. It is expressed
on mammary gland epithelium and on the enterocytes of newborns
(Chapter 23).

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