SEQUENCE VARIATION OF A NOVEL HEPTAHELICAL LEUKOCYTE RECEPTOR THROUGHALTERNATIVE TRANSCRIPT FORMATION

Chemoattractants, including chemokines such as interleukin 8 (IL-8) an d related proteins, activate leucocytes via seven-transmembrane-domain G-protein-coupled receptors. A cDNA for a novel receptor of this kind consisting of 327 amino acids was isolated from a human blood monocyt e cDNA library. The polypeptide, termed monocyte-derived receptor 15 ( MDR15), is an alternative form of the Burkitt's lymphoma receptor 1 (B LR1) encoded by a human Burkitt's lymphoma cDNA [Dobner, Wolf, Emrich and Lipp (1992) fur. J. Immunol. 22, 2795-2799]. MDR15 and BLR1 cDNAs differ in the 5' region, where the open reading frame of MDR15 is shor ter by 45 codons. Southern-blot analysis indicates that the two transc ripts for MDR15 and BLR1 are encoded by the same gene. Northern-blot a nalysis using a probe that hybridizes with both mRNAs demonstrated hig h-level expression in chronic B-lymphoid leukaemia and non-Hodgkin's l ymphoma cells and, to a lesser extent, peripheral blood monocytes and lymphocytes. Reverse transcription-PCR studies with MDR15- and BLR1-sp ecific primers showed similar levels of transcripts for both receptors in RNA that was positive in Northern-blot analysis. MDR15 and BLR1 ha ve high structural similarity to receptors for human IL-8 (about 40 % amino acid identity) and other chemokines. However, none of a series o f radiolabelled chemokines (IL-8, NAP-2, GRO alpha, PF4, IP10, MCP-1, MCP-2, MCP-3, I-309, RANTES and MIP-1 alpha) and other ligands (C3a an d leukotriene B-4) bound to Jurkat transfectants that stably expressed either MDR15 or BLR1 mRNA. The fact that MDR15 and BLR1 are expressed on leucocytes and show marked sequence similarity to chemokine recept ors suggests the existence of as yet unidentified chemokines. Alternat ive transcript formation affecting the 5'-terminal part of the coding region may be a way to modify ligand-binding selectivity.