Prior to the Neutralization assay, 500 mL antisera (diluted 1:50, and pre-absorbed with induced yeast cells carrying the control vector pCTCON-2) were mixed with freshly induced yeast cells (1610 8 ) displaying specific antigenic peptides on surface. After incubation at 4uC for 12 h, the mixtures were centrifuged at 8,000 g for 1 min and supernatants mixed with another batch of freshly induced yeast cells. This process was repeated four times, and then the supernatants were used for determining the neutralization titers, using a microneutralization assay with A/reassortants/NYMC X-179A/California/07/ 2009(H1N1) virus and MDCK cells according to standard procedures [41] . Briefly, triplicate serial dilutions (1:50 to 1:1600) of antiserum samples were incubated with 100 50% tissue culture infective dose (TCID 50 ) of virus for 2 h at 35uC prior to adding MDCK cells. Cells were incubated at 35uC for 72 h, and the half maximal inhibitory concentration (IC 50 ) was determined. All the neutralization assays were performed at the AIDS Research Center, School of Medicine, Tsinghua University following standard procedures. Figure S1 Schematic outline of the screening approach. In Step 1, the gene encoding the viral protein H1N1 HA was amplified, digested and re-assembled to generate the fragment library (the red and grey segments indicate the antigenic and nonantigenic peptides, respectively). In Step 2, the fragment library was ligated into the display vector pCTCON-T, transformed into yeast cells and induced for expression. In Step 3, the yeast cells expressing random peptides were incubated with antisera and fluorescence-labeled second antibodies and subjected to FACS in Step 4. Afterward in Step 5, the gene fragments were isolated from the sorted cells and sequenced. The in-frame sequences were retransformed into yeast cells and verified by FCM detection individually. In Step 6, an antigenic peptide profile was extracted for the sequences corresponding to the antigenic peptides, based on which the residue frequency and structural frequency maps were derived in Step 7. (TIF) [15] . The x-axis represents all H5N1 HA amino acid residues. The y-axis shows the normalized frequency of individual residue appearing in the 784 antigenic peptides (39 unique sequences) obtained from panning against H5N1 avian influenza convalescent sera. The six clusters (I-VI) defined by Khurana et al. are graphically represented below the x-axis. Several representative antigenic peptides are also shown as green arrows (numbered according to Khurana et al.) . Even though the antigenic peptides were enriched multiple times during the screening process and thus these peptides are less diverse and might be biased in sequences, several peaks are clearly identifiable, and predominantly in the HA2 region. (TIF)  New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, “friendly fire” is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects. The complement system was first recognized in the late 19th century when leading microbiologists such as Paul Ehrlich, Jules Bordet and George Nuttall discovered a bactericidal function of blood on anthrax bacilli (1) (2) (3) (4) . They noted that this bactericidal function was inactivated when blood was heated up to 55°C or kept at room temperature and named it "alexin."