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1144 Part IX: Lymphocytes and Plasma Cells

TABLE 73–2. Ectoenzymes Expressed by Lymphocytes
Surface Molecule Enzymatic Activity Function Reference
CD10 Neutral endopeptidase, Metalloproteinase that may also play a role in the metabolic stability of 76
EC 3.4.24.11 glucagon-like peptide-1
CD13 Aminopeptidase N, EC Aminopeptidase involved in trimming peptides bound to major his- 102
3.4.11.2 tocompatibility complex class II molecules and cleaving macrophage
inflammatory protein (MIP)-1 chemokine to alter target cell specificity.
Also served as Rc for coronavirus
CD26 Dipeptidylpeptidase IV, Serine peptidase that may be involved in T-cell signaling and T-cell 77
EC 3.4.14.5 activation
CD38 ADP ribosyl cyclase, Ectoenzyme with NAD glycohydrolase, ADP ribosyl cyclase, and cyclic 74
EC 3.4.14.5 ADP ribose hydrolase activities
CD39 Ecto (Ca , Mg )-apyrase Ectoenzyme with ADPase and ATPase activities that plays a role in regulat- 103
2+
2+
(ecto-ATPase) ing platelet aggregation
CD73 Ecto-5′-nucleotidase Ecto-5′-nucleotidase that may play a role in T-cell signaling 69
CD143 Peptidyl-dipeptide hydro- Peptidyl-dipeptide hydrolase that is involved in the metabolism of vaso- 104
lase (angiotensin-converting active peptides angiotensin II and bradykinin
enzyme)
CD156a ADAM8 metalloprotease Matrix metalloprotease that may play a role in leukocyte extravasation 78
CD156b ADAM17 metalloprotease Metalloprotease that cleaves membrane-bound tumor necrosis factor and 79
transforming growth factor-α to release the soluble cytokine
CD157 ADP ribosyl cyclase and ADP ribosyl cyclase and cyclic ADP ribose hydrolase that may play a role 105
cyclic ADP ribose hydrolase in lymphocyte development. Like CD38, this enzyme also is involved in
the metabolism of NAD
CD224 γ-Glutamyltranspeptidase, γ-Glutamyltranspeptidase role in γ-glutamyl cycle involving the degrada- 106
EC2.3.2.2 tion and neosynthesis of glutathione
ADAM, a disintegrin and a metalloprotease; ADP, adenosine 5′-diphosphate; ADPase, adenosine 5′-diphosphatase; ATPase, adenosine
5′-triphosphate; CD, cluster of differentiation; NAD, nicotinamide adenine dinucleotide.

catalytic activity of CD26 can provoke many cellular effects, including zeta-associated protein of 70 kDa (ZAP-70), leukocyte tyrosine kinase
induction of tyrosine phosphorylation and p38 mitogen- activated protein (lck), or fyn. ZAP-70 interacts with the ζ-chain (CD247) of the TCR
kinase activation, as well as suppression of DNA synthesis and reduced for antigen, whereas the latter enzymes, lck and fyn, are Src family
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production of various cytokines. As such, these ectoenzymes could play tyrosine kinases that interact with cytoplasmic domains of various
an important role in lymphocyte activation. accessory molecules, including CD2, CD4, CD8, CD44, CD50, and/
Some membrane-bound proteases have a disintegrin and a or CD137. Through such interactions, these receptor protein tyrosine
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metalloprotease domain, termed ADAM (a disintegrin and a metallo- kinases play important roles in signal transduction following immune
protease). One such member of this family of proteins is the tumor recognition and/or cognate intercellular immune interactions.
78
necrosis factor-α converting enzyme, otherwise known as ADAM17 In addition, lymphocytes possess an important class of intracellular
(CD156b). These enzymes cleave other surface molecules, such as molecules, known collectively as adapter proteins, that have no intrinsic
79
tumor necrosis factor, thereby releasing the soluble active cytokine. In enzymatic activity. These adaptor proteins can serve as a scaffolding
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addition, they may play an important role in modifying the activity of for the assembly of kinases and other signaling molecules following
cytokines or other cell-surface molecules that are present in the vicinity antigen-receptor ligation. One important adaptor protein expressed in
of the plasma membrane. B lymphocytes is B-cell linker protein (BLNK; Chap. 75). On the other
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hand, T cells use a distinct adaptor protein called linker for activation
Intracellular Membrane-Associated Enzymes of T cells (LAT). These molecules couple proximal biochemical events
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Transmembrane proteins that have cytoplasmic regions with kinase or initiated by surface-receptor ligation with more distal signaling path-
phosphatase activities are common in biology although relatively few ways by recruiting other cytosolic proteins (Chaps. 75 and 76).
of these are restricted to lymphocytes. Nevertheless, many cytoplasmic
domains of transmembrane proteins interact directly with enzymes
that are restricted or preferentially expressed by lymphocytes or lym- CYTOPLASMIC STRUCTURES
phocyte subsets (Chaps. 75 and 76). B lymphocytes, for example, selec-
tively express Bruton tyrosine kinase (BTK), a tyrosine kinase that plays CYTOMATRIX
a critical role in signal transduction via surface Ig receptors. More- Beneath the lymphocyte’s plasma membrane is a fully developed cytoma-
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over, mutations that disrupt the function of such kinases can impair trix with several different structural and mechanical proteins, including
B-cell development, leading to dysregulated B-cell function or immune tubulin, actin, myosin, tropomyosin, α-actinin, filamin, and a spectrin-
deficiency. On the other hand, T-cell development and function rely like molecule, which are important in the formation of the immunologic
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heavily on cytoplasmic receptor-associated tyrosine kinases, such as the synapse that forms during cognate intercellular interactions. These are

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