Murine and human leukocytes express surface glycoproteins, termed homing receptors (HRs), containing lectin-like, EGF-like (egf), and complement binding-like domains, that apparently endow these cells with the ability to home to peripheral lymph nodes (pln's) by virtue of an adhesive interaction with the pln postcapillary venule endothelium. The murine pln HR was initially characterized with a rat monoclonal antibody, Mel 14, that was specific for the murine form of the receptor. This work demonstrated that Mel 14 blocked the binding of murine lymphocytes to pln endothelium both in vitro and in vivo, a result consistent with the possibility that this monoclonal antibody recognizes a region of the HR that is involved with endothelium recognition and adhesion. In addition, this antibody also blocked the binding to the HR of PPME, a polyphosphomannan carbohydrate known to inhibit lymphocyte-pln endothelium interactions, suggesting that Mel 14 may recognize the lectin domain of the pln HR. Here we show that, while Mel 14 recognized truncated HR containing both the lectin and egf domains, antibody recognition was lost when the lectin domain alone was expressed. Chimeric molecules, in which regions of the lectin domain of the non-Mel 14-reactive human pln HR were replaced with homologous regions of the murine pln HR, demonstrated that the Mel 14 recognition site is within the NH2-terminal 53 amino acids of the lectin domain. These results suggest that the Mel 14 monoclonal antibody recognizes a determinant within the lectin domain of the pln HR whose conformation may be dependent upon the presence of the egf domain. Since Mel 14 efficiently blocks lymphocyte-endothelial interactions, these results support the hypothesis that the pln HR lectin domain may be directly involved with binding of lymphocytes to a carbohydrate ligand on the pln postcapillary venule endothelium.

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