The Ly-1.1 and Ly-1.2 epitopes of murine CD5 map to the membrane distal scavenger receptor cysteine-rich domain.

CD5 is a member of a superfamily of proteins which contain one or more extracellular domains homologous to the type I macrophage Scavenger Receptor cysteine-rich (SRCR) domain. The extracellular region of CD5 is composed of three SRCR domains (D1, D2, D3). Murine CD5 (mCD5) is polymorphic (Ly-1.1 and Ly-1.2 alleles), however, the only murine CD5 gene characterized to date encodes the Ly-1.2 allele (mCD5.2). Likewise, the domain specificity of many of the available anti-mCD5 mAb recognizing either Ly-1.1 or Ly-1.2 or both has not been examined. Herein we describe the isolation and characterization of cDNA encoding the Ly1.1 allele (mCD5.1) and map the location and molecular nature of the mCD5 allelic variation. We also determined which SRCR domain of mCD5 is recognized by a panel of anti-mCD5 mAb. The mCD5.1 protein differs from mCD5.2 in only three amino acids, all of which map to the most amino terminal SRCR domain (D1) of mCD5. An additional seven silent substitutions were observed in the nucleotide sequence encoding mCD5 D1, D2 and transmembrane domains. Immunoglobulin (Ig) fusion proteins consisting of various combinations of mCD5.1 or mCD5.2 SRCR domains were produced and used to determine that allele specific mAb bound to D1, confirming sequence data. MAb against monomorphic determinants on mCD5 bound to each mCD5D11g.