Lecture 20 - T Cell Activation

Route of circulation for mature naive T cells

  • mature naive T cells exit the thymus into the bloodstream to secondary lymphoid organs like lymph nodes via HEVs

  • they migrate to the T cell zone and interact with dendritic cells

    • antigen recognition will activate the T cell

    • no antigen recognition prompts exit via the efferent lymphatic vessel to the next lymph node

  • naive T cells can enter a draining lymph node by two routes:

    • in the blood

    • in the afferent lymph coming from an upstream lymph node

  • secondary lymphoid tissues collect antigens

Dendritic cells in the circulation of T cells

  • dendritic cells bring antigen to lymph nodes via lymphatics

    • they phagocytose microbes and antigens at local sites

    • they are activated by PAMPs at local sites

      • express more MHC molecules

      • express co-stimulatory molecules for T cell activation (B7)

    • migrate into lymph nodes following chemokine gradient

  • these dendritic cells diff from follicular dendritic cells

  • T cells and dendritic cells meet in secondary lymphoid tissues

T cell Activation

1) MHC - TCR with co-receptor (either CD4 or CD8)

  • dendritic cell — MHC molecule presenting antigen

  • T cell — TCR, CD3 complex, co-receptor

2) Co-stimulatory signal

  • B7 - CD28

  • B7 is expressed on dendritic cells activated by PAMPs

  • the only other cells that can express B7 are macrophages and B cells, but these must be activated by T cells to express this molecule

  • dendritic cell — B7, expression induced when PRRs are activated by PAMPs, B cells express when activated so that they can establish the conjugate pair

  • T cell — CD28 & all naive T cells express CD28

  • T cell activation requires co-stimulation

    • T cells always require co-stimulation to activate, regardless of MHC class

    • dendritic cells express B7 ligand only after recognizing a PAMP

    • no co-stimulation = anergic T cell

  • peripheral tolerance — requirement of B7 co-stimulatory signal serves to negatively select T cells that bind to antigen presented by activated dendritic cells

    • only professional APCs can express B7 (macrophages, neutrophils)

3) Cytokine activation

  • IL-2

  • additional cytokine secretion defines T cell phenotype/functions

  • T cells — activated by MHC-antigen and co-stimulator

    • express high affinity receptor for IL-2 & secrete IL-2

    • IL-2 has autocrine signaling which induces T cell proliferation

After signal 1 & 2 have been completed:

  • once activated by the first 2 signals, the T cell will secrete IL-2 and express high affinity receptor for IL-2

Antigen cross-presentation