Discriminating intrinsic and antigen-selected mutational hotspots in immunoglobulin V genes.
Studies of the antibody hypermutation mechanism have revealed that it is not a random process but exhibits characteristic nucleotide substitution preferences. Here, Alexander Betz and colleagues show that these innate nucleotide substitution preferences can be used to examine databases of antigen-selected V gene sequences and thereby distinguish intrinsic from antigen-selected hotspots. This analysis reveals intrinsic mutational hotspots in both VH and VL genes, reflecting innate features of the hypermutation machinery which may give clues to the enzymatic mechanism.
Betz
A G
AG
Medical Research Council Laboratory of Molecular Biology, Addenbrookes Hospital, Cambridge, UK.
Neuberger
M S
MS
Milstein
C
C
D000818:Animals; D000941:Antigens / Q000235:genetics*; D001483:Base Sequence; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
D000941:Antigens; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region