Branzyme B
A key
function of human granzyme B (GrB)
is to induce apoptosis of target cells, in conjunction with perforin.
The RAH allele is the first documented variant of the human GrB
gene, and occurs at frequency of 25-30%. It encodes three amino acid
substitutions (Q48R, P88A, Y245H). It was initially
reported that RAH GrB is incapable of inducing
apoptosis, but here we show that it has essentially identical proteolytic and cytotoxic
properties to wild type GrB. Recombinant RAH and wild
type GrB cleave peptide substrates with similar
kinetics, are both capable of cleaving Bid and procaspase
3, and are equally inhibited by an endogenous regulator of GrB,
PI-9. Furthermore, cytotoxic lymphocytes from RAH heterozygotes and homozygotes
have no defect in target cell killing, and in vitro RAH GrB
and wild type GrB kill cells equally well in the
presence of perforin. We conclude that the RAH allele
represents a neutral polymorphism in the GrB ge
PMID: 14752093 [PubMed - as supplied by publisher]