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Extra resources for Annual Review of Immunology Volume 26 2008

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Also, the role of LYP in the autoantibody response may not necessarily be intrinsic to B cells but rather a consequence of altered T cell help. The uncertainty regarding which cells are phenotypically affected by LYP∗ W620 in different disease settings is further exemplified by a recent study demonstrating that carriers of the T1858 allele are more prone to certain infectious diseases, such as invasive pneumococcal infections and Gram-positive empyema (79). These findings may reflect reduced antibody responses owing to the presence of LYP∗ W620 in B cells, or they may even be caused by the effects of LYP∗ W620 in neutrophils.

Most likely, the binding between disease-associated CD2BP1 and LYP/PTP-HSCF is affected Annu. Rev. Immunol. 26:29-55. org by Shanghai Information Center for Life Sciences on 04/28/08. For personal use only. PTK: protein tyrosine kinase 40 Vang et al. in a similar way. C-terminal to the coiledcoil domain, CD2BP1 contains an SH3 domain that interacts with CD2, Abl, and WASP (Wiskott-Aldrich syndrome protein). Notably, the CD2/CD2BP1/PTP-PEST complex negatively affects T cell responses (89). Similarly, the CD2BP1/PTP-PEST complex also exists in other hematopoietic cells, and the disruption of this complex in neutrophils from FRA/PAPA syndrome patients is most likely the underlying cause for the accumulation of dysfunctional neutrophils in the affected organs in this disease (88).

Mustelin, unpublished observations). The subcellular localization of LYP is mainly cytoplasmic, but some PEP can also be found in the nucleus (20, 24). Factors determining the localization of LYP/PEP in cells are poorly understood, but several binding partners have been identified. The best characterized is C-terminal Src kinase (Csk), which through its Src homology 3 (SH3) domain binds to the P1 region in LYP/PEP (25–27). This interaction is of relatively high stoichiometry: In mouse T cells, approximately 5% of total cellular Csk associates with 25% to 50% of total cellular PEP (25); the corresponding numbers for LYP in human cells are not known.

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