Figure A: Signal transduction in T cells: mutations identified in severe combined immunodeficiency (SCID) and combined immunodeficiency (CID) patients.

(left) The diagram depicts molecules involved in signal transduction in T lymphocytes. Mutant proteins implicated in the pathogenesis of human SCID are highlighted in red. Jak3, janus kinase 3; IL-2Rg, interleukin 2 receptor g chain (common g chain, cg); CRAC, calcium release activated calcium channel; ZAP-70, zeta-associated protein 70; NFAT, nuclear factor of activated T cells; PLCg, phospholipase C g; ER, endoplasmic reticulum.

(right) The presence or absence of T, B or NK cells in the various forms of SCID and CID is indicated. Where the symbol is crossed out, no cells are detectable. Low total T cell numbers, low CD4+ and low CD8+ cell numbers, respectively, are indicated by small circles. The arrow in the green box symbolizes T cell activation; were crossed out, T cell activation is partially (light red) or severely (dark red) impaired. E.g. patients with a mutation in ZAP-70 have low to undetectable numbers of CD8+ T cells but CD4+, B and NK cell counts are normal. However, activation of CD4+ cells is severely compromised.