Isolation of a cDNA clone encoding a novel form of granzyme B from human NK cells and mapping to chromosome 14.

We have isolated cDNA clones from a human NK cell cDNA library that encode the serine protease granzyme B. Although the sequence of the entire coding region for the mature protein and the 3' untranslated region of the clone are identical to other cDNA isolates of this gene obtained from human T cell cDNA libraries, the 5' end of two clones is 103 bp longer than the previously described sequences and would encode a protein with a 54-amino-acid-long signal sequence. Experiments characterizing granzyme B mRNA suggest that transcripts that initiate at or before the 5' end of these clones comprise a detectable but infrequent class of granzyme B transcripts in NK and T cells. We have mapped this gene to human chromosome 14 in the region 14q11----14q32, distal to the T cell receptor alpha locus and proximal to the immunoglobulin heavy chain locus. The chromosomal location of this gene, together with the previously described high sequence homology between this gene and the mouse CTLA 1/ccp1 gene, make it likely that this is the human equivalent of the mouse CTLA1/ccp1.