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chapter35

Molecular Immunology

F I G U R E 3 5 - 1 7

(Also see color figure.) Complex of HIV gpI20, Fab fragment, and CD4. HIV gpl20 is an envelope protein of HIV-1

that is exposed on the outer surface of the virus. It is derived from gpl60 by proteolysis that also produces another

product, gp41. Only a small area of the surface of the gp 120 and CD4 molecules is in contact. Interaction between CD4

and gpl20 is dominated by residues Phe43 and Arg59 of CD4, and Gly370, Try427, and Asp368 of Gpl20. The

antibody fragment blocks the region of gpl20 that interacts with a chemokine receptor, CCR5. The figure is derived

from the coordinates published in the Protein Data Bank file IGC1.

permits infections by microorganisms that are not nor-

mally pathogenic, e.g.,

Pneumocystis carinii,

to occur.

35.8 Antibody Diversity and

Immunoglobulin Genes

The enormously large number of epitopes on antigens

that must be recognized so that an organism can success-

fully defend itself from disease requires the existence of

a comparable diversity of antibodies and antigen recep-

tor molecules. Because each immunoglobulin molecule

and T-cell receptor is produced by separate clones, mech-

anisms for generating such diversity are necessary. It is

estimated that there are more than

1 0 0

trillion (>

1 0

14)

different B- and T-cell clones. The genes that code for

the immune system molecules are capable of recogniz-

ing and interacting with the very large number of different

epitopes. These are “created” during embryonic differenti-

ation. The genetic mechanisms required to meet this need

for diversity and adaptability are unique to the immune

system.

There are three families of immunoglobulin genes: one

for

k

light chains, one for A

. light chains, and one for the

heavy chains (see Table 35-2). Within each of these fam-

ilies are germline genes that contain many different ex-

ons that code for the constant regions in chains of the

immunoglobulin classes and for the variable regions that

are responsible for epitope recognition. By combinato-

rial recombination of the different exons present in the

germline genes, the genes are created that code for both

immunoglobulins and the T-cell receptors that recognize