## 1 Introduction  
The ability of the immune system to provide an efficient response against pathogens without hyper reacting against host tissues relies on a tight balance between pro- and anti-inflammatory signals. Disruption of this equilibrium can lead to autoimmunity. C1q, a protein initially identified as the recognition protein that triggers the classical pathway of the complement system, has been shown to play a major role in the maintenance of immune tolerance [1]. Indeed, homozygous deficiencies in C1q are strongly associated with severe autoimmune inflammatory diseases such as systemic lupus erythematosus (SLE) (>90% prevalence) [2]. C1q is a multimeric protein composed of 18 polypeptide chains of types A, B and C. Assembled in six heterotrimers maintained by both noncovalent and covalent interactions, these chains are composed of a short N-terminal part containing interchain disulfide bonds (between A-B and C-C), followed by a collagen-like region (CLR) containing the characteristic repeating G-X-Y triplets (X being any amino acid and Y a proline or hydroxyproline residue) and a C-terminal globular region (GR) [3]. This complex assembly leads to the formation of a 460 kDa C1q protein with a \"bouquet-like\" structure, where six C-terminal globular domains are connected via six collagen stems gathered in an N-terminal fiber bundle [4, 5]. Functional studies revealed distinct activitiesfor the GR and CLR of C1q. On one hand, the globular regions are mostly involved in the recognition of several targets like antibodies Fc region, molecules on pathogens surfaces or altered-self components [6; 7]. On the other hand, the collagen-like regions of C1q are engaged in immune response effector mechanisms through their interaction with a tetramer of complement C1r and C1s proteases (C1r\({}_{2}\)s\({}_{2}\)) or receptors on immune cells surface [8; 9]. Leukocyte associated immunoglobulin-like receptor 1 (LAIR-1; CD305) is an inhibitory receptor of 32 kDa expressed on many types of immune cells and composed of an extracellular C2-type immunoglobulin-like (Ig-like) domain, a single transmembrane segment and a cytoplasmic tail containing two immunoreceptor tyrosine inhibitory motifs (ITIMs) [10; 11]. It is well established that LAIR-1 is a receptor for a large range of collagen types, from extra cellular matrix and transmembrane collagens (such as collagens I, II, III, IV, XIII, XVII or XXIII) to collagen-containing proteins such as surfactant protein D (SP-D), mannose-binding lectin (MBL) or C1q. LAIR-1 activation by one of these identified ligands leads to its ITIMs phosphorylation, recruitment of SHP-1 tyrosine phosphatase and inhibition of proinflammatory signals [12; 13; 14; 15; 16]. Human LAIR-1 has a soluble homologue LAIR-2 shown to interact with the same ligands and supposed to control LAIR-1 inhibitory activity by competing for collagen binding [12; 13; 17]. LAIR-1 is the only known inhibitory receptor of C1q CLR and [PERSON] and colleagues have reported that it is an important mediator of C1q-mediated immune tolerance, together with other immune receptors such as CD33 and the receptor for advanced-glycation end-products (RAGE) [14; 18; 19]. Due to its multimeric nature, C1q would likely interact with several of these receptors simultaneously, thus generating local gathering of pro- and anti-inflammatory signals. However, these processes remain unclear and the molecular and structural determinants of C1q interaction with these receptors have not yet been identified. In the present study, we aimed at deciphering the molecular basis of C1q/LAIR-1 interaction. To do so, we produced recombinant soluble LAIR-1 Ig-like domain and tested its interaction properties for C1q by surface plasmon resonance (SPR). We showed that C1q interacts with LAIR-1 via its CLR on a binding site close to, but different from the one of C1r\({}_{2}\)s\({}_{2}\). On LAIR1, mutational analyses allowed the identification of several key residues involved in C1q interaction.