Innate lymphoid cells & unconventional T-cells

γδ T-cells

NK T-cells

MAIT

TCR expressing cells

not restricted by classical MHC molecules

activation not dependent on coreceptors

cytotoxic

express TCR & play innate-like immune functions (mostly inflammatory cytokines & cytotoxicity)

heterdimer of γ chain & δ-chain

(in conventional TCR alpha and ß-chain)

compared to conventional receptor less diversity (smaller number of genes for the different regions)

alpha = gamma

beta = delta

common progenitor with conventional T-cells

choice for γδ in thymus at DN3 stage

predominant before birth in embryonic tissues, waves of peripheral colonization (first to be generated during development)

γ chains define differnet peripheral tissue that is colonized —>tissue specific ligands present?

TCR γδ Vδ1+: predominant in thymus and spleen

TCR γδ Vδ2+: predominant in peripheral blood, mainly associated with Vδ9 TCR chain, 30-100% of γδ in blood and 1/20 of blood T cells

TCR γδ Vδ3+: liver/epithelial

MHC related proteins (MICA/B)

stress molecules: ULBP4 (Vγ9Vδ2), CD1 (Vδ1)

phosphoantigens, amino-bisphosphonates (Vγ9Vδ2)

CD1 molecules presenting lipids (see NK-T)

MHC releated

CD1b expressed by DC

CD1c expressed by B cells and DC

CD1d wide pattern of expression on hematopoietic and non-hematopoietic cells

activated by phosphorylated antigens

phosphorylated antigen bind to BNT3A1 inducing conformational changes

—>activates ectodomian of BTN3A1 for TCR binding

—>cytotoxicity and cytokine release

BTN3A is a B7-like molecule (needed for activation of conventional T-cells), immunoglobuline superfamily

(phoshporylated antigens could be used in antitumor therapy)

T-cells expressing alpha/beta TCR

expression of NK receptors

behave as NK cells (immediate reactivity—>innate immunity)

some are CD4+

no need for CD4 to get activated

—>most invariant only expressing Vα24 in humans (and variable ß-chain)

CD1d restricted (MHC related molecule)

binds α-galactoceramide (glycolipid) self

—>others restricted by CD1a,b,c

more diverse

recognize glycolipid from microbes

Mucosa associated invariant T-cells

invariant α-chain 1 or 2

abundant in the lamina propria (gut mucosa)—>40% of all T-cells

0,1-10% blood T-cells

restricted by MR-1 molecule —>MHCI related, associated with ß2m, gene outside MHC locus

presented antigens: metabolites used by bacteria & yeast (e.g. riboflavin)

loaded in the ER

MAIT express CD8αα (normally heterodimer αß)

classical HLA (conventional TCR)

MHC related, non-classical MHC

metabolite (much smaller)

large lipids

unconventional B-cells

express BCR producing constitutively natural Abs with high cross reactivity

B1 cells produced earlier, less diverse, self renewing (stem B1 cells), produce natural antibodies with high cross-reactivity (dont need activation & continous Ab production), recognize antigens with sugars, dont collab with T&B-cells, cant increase affinity to antigen due to mutations in variable chain

group 1: NK cells + ILC1

group 2: ILC2

group 3: ILC3

lymphocytes without expression of a TCR/BCR playing diverse innate-like immune functions (only NK cells cytotoxic)

no expression of a rearranged antigen receptor (TCR/BCR)

defiend by their cytokine secretion profile—>have diverse functions

some are cytotoxic (NK cells)

cytotoxic

activated by IL-12 from virus infected or intracellular bacteria cells

produce IFNγ (TH1 like)

TH2 like function controlling parasite infection

activated by TSLP, IL-33, IL-25 from host cell

secretes IL-13 & IL-5

TH17 like function

activated by IL-23 from extracellular bacteria

secrete IL-17 and IL-22

flow cytometry to identify cell population

for unconventional cell exclude lineage specific marker

discrimination of different populations via morphology (SSC) and size (FSC)

CD3

CD19

CD14

CD56

CD15