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Group S. Kliche

Research Profile

Attachment of T cells to the endothelium and subsequent extravasationIntegrins, like VLA-4 or LFA-1 (ß1 and ß2 integrins, respectively) are critical important for the induction of an adaptive immune response. Both integrins play important roles during T-cells-mediated adhesion to the endothelium, an event that is essential for the migration and extravasation of T-cells. LFA-1-mediated adhesion also establishes and strengthens the contact between T-cells and antigen presenting cell (APC). However, both VLA-4 and LFA-1 are not constitutively adhesive. Rather, external stimuli (e.g. binding of antigen to the TCR or binding of chemokines to their corresponding receptors) trigger the activation of integrins and enhance their affinity for the corresponding ligands, ICAM and VCAM (inside-out signaling). Two cytosolic adapter proteins SKAP55 and ADAP have been identified that seem to be involved in this signaling processe in T-lymphocytes.

ADAP is required for efficient induction of ß1 and ß2-mediated adhesion. Thus, TCR-stimulated clustering of the ß2 integrin LFA-1 is defective in ADAP-deficient mice. The loss of TCR-induced LFA-1 clustering in the absence of ADAP is consistent with known interactions of integrins with the cytoskeleton. Overexpression approaches of either ADAP or SKAP55 have further implicated a role of both adapter proteins for the T-cell-APC conjugate formation and T-cell migration. ADAP constitutively interacts with the T-cell-specific adapter protein SKAP55. Like ADAP, SKAP55 potently increases T-cell-APC conjugate formation and T-cell migration when overexpressed in T-cell lines. The comparable participation of ADAP and SKAP55 in inside-out signaling events of ß1 and ß2 integrins and their comparable effects on T-cell adhesion and migration is consistent with the idea that both molecules form a functional unit in T-cells. How SKAP55 and ADAP activate integrins are not fully understood and will be studied in this group.


Kliche, Dr. rer. nat. Stefanie