Coordinated expression of DNAM-1 and LFA-1 in educated NK cells

• The functional capacity of NK cells is dynamically tuned by integrated signals from inhibitory and activating cell surface receptors in a process termed NK cell education. However, the understanding of the cellular and molecular mechanisms behind this functional tuning is limited. In this study, we show that the expression of the adhesion molecule and activation receptor DNAX accessory molecule 1 (DNAM-1) correlates with the quantity and quality of the inhibitory input by HLA class I-specific killer cell Ig-like receptors and CD94/NKG2A as well as with the magnitude of functional responses. Upon target cell recognition, the conformational state of LFA-1 changed in educated NK cells, associated with rapid colocalization of both active LFA-1 and DNAM-1 at the immune synapse. Thus, the coordinated expression of LFA-1 and DNAM-1 is a central component of NK cell education and provides a potential mechanism for controlling cytotoxicity by functionally mature NK cells.

Subject headings

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

Keyword

alpha interferon

CD94 antigen

cell adhesion molecule

cell adhesion molecule LFA 1

DNAX accessory molecule 1

HLA E antigen

interleukin 12

interleukin 15

interleukin 18

interleukin 2

interleukin 21

killer cell immunoglobulin like receptor

natural killer cell receptor

natural killer cell receptor NKG2A

natural killer cell receptor NKG2D

unclassified drug

antigen expression

antigen presentation

antigen presenting cell

antigen recognition

Article

cell maturation

cellular distribution

conformational transition

controlled study

cytokine production

cytokine release

cytolysis

effector cell

human

human cell

immunological memory

immunological synapse

immunoregulation

lymphocyte differentiation

natural killer cell

priority journal

protein determination

protein expression

protein function

protein localization

protein protein interaction

protein targeting

receptor intrinsic activity

signal transduction

Publication and Content Type

ref (subject category)

art (subject category)