Although this could substantially reduce the quantity of protein required for the successful generation of TCR/pMHC complex crystals capable of diffracting to high resolution, our analyses revealed that a limited screen could exclude some important crystallization conditions for some proteins. PF-02341066 solubility dmso Thus, our TOPS screen remains optimal for the crystallization of TCR/pMHC complexes. In conclusion, we hope that TOPS will greatly contribute to a better understanding of molecular basis for T cell recognition of self, foreign (microbial/viral/parasitic) and autoimmune antigens
by providing an improved method for generating TCR/pMHC complex protein crystals capable of high quality X-ray diffraction. Furthermore, we expect that TOPS will be useful for the determination of TCR structures in complex with classical and non-classical MHC ligands that are less well characterized, including: pMHC class II, MR1, CD1c and HLA-E. Structural information, detailing the precise atomic contacts that mediate T cell immunity, can provide clear insights into various immune dysfunctions
and could accelerate the rational design of T cell based therapies and vaccines. D.K.C., C.J.H., P.J.R., A.J.A.S., A.F., A.M.B and F.M., GDC-0941 cost performed experiments, analyzed data and critiqued the manuscript. D.K.C., and P.J.R., conceived and directed the project. F.M., A.M.B., D.K.C., A.K.S., and P.J.R., wrote the manuscript. The authors declare no competing financial interests. No animals were used in this study. All human samples were used in accordance with UK guidelines. We thank the staff at Diamond Light Source for providing facilities
and support. FM is funded by a Tenovus PhD studentship. DKC is a Wellcome Trust Research Career Development Fellow (WT095767). PJR was supported by a RCUK mafosfamide Fellowship. “
“Collectin 11 (CL-11), also known as collectin kidney 1 (CL-K1), belongs to the collectin group of the innate immune molecules structurally characterized by containing a carbohydrate recognition domain and a collagen-like region (Keshi et al., 2006). CL-11 is ubiquitously expressed, but highest levels are found in the adrenal glands, the kidneys, and the liver, and it is also present in circulation (Hansen et al., 2010). It is highly conserved among species ranging from zebrafish to humans. CL-11 has been shown to bind to intact bacteria, fungi and influenza A virus, and also to decrease influenza A infectivity. CL-11 was found to be associated with mannose-binding lectin-associated serine protease 1 (MASP-1) and/or MASP-3 in plasma (Hansen et al., 2010). These findings indicate a role for CL-11 in the defense against pathogens and in the activation of the complement system. Recently, CL-11 and MASP-3 were shown to be involved in fundamental developmental processes.