Immunogenetic analysis of the heavy chain variable regions of IgE from patients allergic to peanuts.
Peanuts are one of the most allergenic of the foods, and hypersensitivity responses to peanut allergens can be fatal. Although the nature of the antigenic components of peanuts is being defined at the molecular level, there is little information on the induced IgE antibodies, which are central to the allergic reaction. Recognition sites of IgE antibody molecules arise from the variable regions of heavy and light chains (VH and VL). By using nested polymerase chain reactions with specific primers for the available repertoire of VH genes, together with primers in the constant epsilon region, we have amplified VH sequences of IgE from blood lymphocytes of two patients with peanut allergy. After cloning and sequencing the products, we found a predominance of VH1 family use in both patients, which was not found in control IgM-specific primers. The IgE VH sequences were highly somatically mutated, but in only six of 17 cases was there clear evidence for clustering of amino acids indicative of antigen selection. Previous results from patients with allergy to house dust mites have indicated predominance of VH5 use and little evidence for antigen selection. Although results from two patients allergic to peanuts must be regarded as preliminary, they do suggest that the IgE response to peanuts may have a different VH bias, with a similar mutational pattern.
Janezic
A
A
Tenovus Laboratory, Southampton University Hospitals, United Kingdom.
Chapman
C J
CJ
Snow
R E
RE
Hourihane
J O
JO
Warner
J O
JO
Stevenson
F K
FK
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D010367:Arachis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005512:Food Hypersensitivity / Q000276:immunology*; D005803:Genes, Immunoglobulin; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007073:Immunoglobulin E / Q000235:genetics* / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007073:Immunoglobulin E