Technical Notes: CCR7

CCR7

CCR7, an orphan receptor formerly known as EBI1 (EBV-induced gene 1),1 is the chemokine receptor for CCL19/ELC/MIP-3 beta and CCL21/SLC/6Ckine.2-4 It is expressed on T cells and dendritic cells (DC), consistent with the chemotactic action of CCL19 and CCL21 for both lymphocytes and mature DC. Both memory (CD45RO+) and naïve (CD45RA+) CD4+ and CD8+ T cells express the CCR7 receptor.5 Within the memory T cell population, CCR7 expression discriminates between T cells with effector function that can migrate to inflamed tissues (CCR7-) vs. T cells that require a secondary stimulus prior to displaying effector functions (CCR7+).5 Unlike mature DC, immature DC do not express CCR7 nor do they respond to the chemotactic action of CCL19.6,7

Figure 1 A Figure 1 B
Figure 1A & 1B. The specificity of an Anti-Human CCR7 Monoclonal Antibody (Catalog # MAB197) was demonstrated by its ability to react with HEK-293 cells transfected with the human CCR7 receptor (A) and for its ability not to react with irrelevant transfectants (HEK-293 cells transfected with the human CCR4 gene) (B). Transfection efficiency was assessed through the use of an EGFP reporter system, which renders transfected cells positive for FL1 signals. Antibody binding was monitored using a goat anti-mouse PE conjugated polyclonal.

A key function of CCR7 and its two ligands is facilitating recruitment and retention of cells to secondary lymphoid organs in order to promote efficient antigen exposure to T cells. CCR7-deficient mice demonstrate poorly developed secondary organs and exhibit an irregular distribution of lymphocytes within lymph nodes, Peyer’s patches, and splenic periarteriolar lymphoid sheaths.8 These animals have severely impaired primary T cell responses largely due to the inability of interdigitating DC to migrate to the lymph nodes.8 The overall findings to date support the notion that CCR7 and its two ligands, CCL19 and CCL21, are key regulators of T cell responses via their control of T cell/DC interactions. CCR7 is an important regulatory molecule with an instructive role in determining the migration of cells to secondary lymphoid organs.8,9

Figure 2 Figure 3
Figure 2. Reactivity of monocyte derived DC stained with a Fluorescein-conjugated Mouse Anti-Human CCR7 Monoclonal Antibody (Catalog # FAB197F), or a Fluorescein-conjugated Mouse IgG2A Isotype Control (Catalog # IC003F). Figure 3. Reactivity of peripheral blood lymphocytes stained with PE-conjugated Mouse Anti-Human CCR7 Monoclonal Antibody (Catalog # FAB197P), or a PE-conjugated Mouse IgG2A Isotype Control (Catalog # IC003P).

References

  1. Birkenbach, M. et al. (1993) J. Virol. 67:2209.
  2. Rossi, D.L. et al. (1997) J. Immunol. 158:1033.
  3. Yoshida, R. et al. (1997) J. Biol. Chem. 272:13803.
  4. Yoshida, R. et al. (1998) J. Biol. Chem. 273:7118.
  5. Sallusto, F. et al. (1999) Nature 401:708.
  6. Sallusto, F. et al. (1998) Eur. J. Immunol. 28:2760.
  7. Dieu, M.C. et al. (1998) J. Exp. Med. 188:373.
  8. Forster, R. et al. (1999) Cell 99:23.
  9. Nakano, H. et al. (1998) Blood 91:2886.