CYTOKINE RECEPTORS

Komal Bhanushali

IntroductionLow molecular weight compounds (<30KDa).Regulate the intensity and duration of immune

response by exerting a variety of effects on lymphocytes & other immune cells.

They are messengers of immune system They mediate biological effects at picomolar

concentrationsFunction mostly by autocrine & paracrine actionInterleukins, monokines, lymphokines,

chemokines,term CYTOKINE include all of them.Cytokines exert their biological effects by

binding to specific receptors expressed on the membrane of responsive target cells

Families5 Major Receptor Families

Immunoglobulin Super familyHematopoietin Receptor Family

(Class I)Interferon Receptor Family (Class II)TNF Receptor FamilyChemokine Receptor Family

Immunoglobulin Super FamilyStructure identical to

immunoglobulin'sReceptors for IL-1,IL-18Role of IL-1:-InflammationReceptors for IL-1 are of two

types :- type1 IL-1R-expressed on many

cells type2 IL-1R-limited to B cells

Hematopoietin Receptor Family(Class 1)Members:-Receptors that function in

immune and hematopoietic systems.Features:-Conserved amino acid sequence

motif in extra cellular domain consisting of 4 cysteines (CCCC) & WSXWS.

Ligands:- -All cytokines classified as hematopoietins -IL2 &1L3 other ILs -Several CSF -Growth hormones

Interferon Receptor Family(Class II)Features:-Conserved CCCC but lack

WSXWS .Family consists of 12 receptor chains that

in their various assortments bind to various cytokines

Ligands:-more than 27 different cytokines including- IFNα,β,γ plus 17 type1 IFNs

-1 type II IFN -3 types of IFN λ -6 members of IL10 family

Subfamilies of Class I cytokine receptorsHave multiple subunits, often including

one subunit that binds to specific cytokine and other that mediates signal transduction.

3 Subfamilies described here:- i)GM-CSF ii)IL2 iii)IL6Exhibit redundancy and antagonism due

to sharing of signal transducing subunit.

1)GM-CSF Receptor Subfamily Common signal transducing

subunit is β subunit & cytokines bind with low affinity to α subunit.

Includes receptors for:- 1)IL3 2)IL5 3)GM-CSF Dimeric receptors.

CONTD… Redundancy :-as β subunit is common.

• IL-3 &GM-CSF together will act on hematopoietic stem cells ,progenitor cells, activate monocytes and induce megakaryocyte differentiation.• IL-3, GM-CSF, IL-5 all these three together will

induce eosinophil proliferation , basophil degranulation with release of histamine

Antagonism:-as they compete for limited number of β subunits.

Interactions between Cytokine-specific Subunits

and a Common Signal-transducing Subunit of

Cytokine Receptors

Signaling

Competition of Ligand-binding Chains of Different Receptors for a Common Subunit Can Produce

Antagonistic Effects between Cytokines

2)IL6 Receptor SubfamilyCommon signal transducing subunit is

gp130 associated with one or two different types of cytokine specific subunits

Includes receptors for:- 1)IL-6 2)IL-11 3)LIF(Leukemia Inhibitory Factor) 4)OSM (Oncostatin M) 5)CNTF (Ciliary Neurotrophic Factor)

CNTF: ciliary neurotrophic factorLIF: leukemia-inhibitory factorOSM: oncostatin M

3)IL-2 Receptor Subfamily Common signaling subunit is γ Includes receptors for :- 1)IL2 2)IL4 3)IL7 4)IL9 5)IL15 6)IL21 IL2&IL15 are heterotrimers rest all are dimers Defect in γ chain gene leads to XSCID(X-Linked

Severe Combined Immuno Deficiency)

CONTD…IL2R main role:-clonal

proliferation of T cells.IL2 occurs in 3 forms :- 1)low affinity monomeric IL-2Rα 2)Intermediate affinity dimeric IL-2Rβγ 3)High affinity trimeric IL-2Rαβγ

3 Forms of the IL-2 Receptor

(CD25)

THANK YOUTHANK YOU