Table 1.

Characteristics of key IL-21 mAbs and the soluble IL-21R/γ_c-Fc heterodimeric receptor

	IL-21R/γc-Fc	Clone 362.78	Clone 362.597	Clone 366.552	Clone 366.328	Clone 362.75	Clone 366.345
Epitope bin	#1	#1	#1	#1/2 (overlap)	#2	#2	#3 (non-neutralizing)
Isotype	n/a	IgG4, kappa	IgG1, kappa	IgG1, kappa	IgG4, kappa	IgG1, kappa	IgG (subtype n.d.)
VH germline gene	n/a	VH3-33	VH3-33	VH4-59	VH3-21	VH4-39	n.d.
VL germline gene	n/a	VkIII A27	VkIII A27	VkI L5	VκI L4	VkIII L6	n.d.
Cross reacts with human IL-2, -4, -7, -9, or -15	n.d.	No	No	No (western blot only)	No (western blot only)	No (western blot only)	n.d.
Inhibits IL-21 binding to soluble homodimeric IL-21R	Yes	Yes	Yes	Yes	No	n.d.	No
Inhibits IL-21 binding to soluble heterodimeric IL-21R/γc	Yes	Yes	Yes	Yes	No	n.d.	No

Cross-reactivity to related γ_c cytokines was assessed by western blot analysis for all mAbs except 366.345. Clone 362.78 was further assessed for cross-reactivity to the related cytokines by surface plasmon resonance, and was also evaluated in bioassays for a subset of these cytokines (IL-2, -4 and -15; see Materials and Methods). Competition for IL-21 binding to soluble receptors was determined by surface plasmon resonance (Fig. 6); n/a, not applicable; n.d., not determined.