J. Clin. Invest. 108: 785–791 (2001). DOI: 10.1172/JCI200114006. some basic structure-function information. Amino acids 93–120 define a minimal high-affinity binding site for TSP-1 that may be modulated by a downstream sequence (amino acids 139–155). Binding of oxidized LDL (oxLDL) has been mapped to a major domain at amino acids 120–155 and a second region with less but significant affinity at amino acids 28–93. The site for binding of apoptotic cells and P. falciparum–infected erythrocytes is proposed to lie between amino acids 155 and 183, but this conclusion is based solely on mAb inhibition. Antibodies to this immunodominant epitope block all known CD36 function, including TSP-1 binding, making it difficult to interpret these results unequivocally. Our laboratory determined that the TSP-1 binding site of CD36 is contained within a highly conserved sequence in CD36 family members that we termed the CLESH (CD36 LIMP-II Emp sequence homology) domain (9), which is also found in other proteins. Interestingly, the type I repeat of TSP-1, the domain containing the CD36 binding site, is also found in many other proteins. Characterizing expression profiles of these domains may identify potential receptorligand pairs. For example, we noted that the gp120 envelope protein of HIV contains a CLESH domain and showed that it binds TSP-1 (10). This knowledge may directly relate to the inhibitory effect on HIV infectivity of saliva, which contains a large concentration of TSP-1, and it may be exploited in the design of drugs to inhibit HIV transmission.