HLA-D gene studies in relation to immune responsiveness to a grass allergen Lol p III.
The grass pollen allergen Lol p III (Mr 11,000) is a well-characterized antigen that has been found useful in immunogenetic studies of human immune responsiveness. Since immune responsiveness to this allergen is associated with HLA-DR3, we investigated whether there was any sequence in the HLA-D region that would render a person "susceptible" [antibody (Ab)-positive] to the allergen. By sequence-specific oligonucleotide (SSO) slot-blot and sequence analyses of polymerase chain reaction (PCR)-amplified genomic DNA from Lol p III responder and nonresponder subjects, Ab responsiveness was found to be strongly associated with the sequence Glu-Tyr-Ser-Thr-Ser (EYSTS), present in the first polymorphic regions of DR beta I polypeptide chains of DR3, DR11 (split of DR5), and DRw6. Of the 41 grass-allergic subjects investigated, 19 had the EYSTS sequence, of whom 18 (95%) were Lol p III immunoglobulin G (IgG) Ab responders; among the 22 EYSTS- subjects, ten were Lol p III responders (P = 0.001, relative risk = 21.6). No such association was found with any polymorphic sequences in other DR beta chains, or in DQ alpha I and DQ beta I chains. These findings suggest that the EYSTS sequence is important in the presentation of an epitope of Lol p III; other sequence(s) may be involved in the presentation of other epitope(s). To our knowledge, this is the first demonstration of a strong association between a specific HLA sequence and immune responsiveness to a well-defined antigen. The paper shows that presence of the EYSTS sequence classifies subjects as Lol p III responders in 18/19 cases.
Ansari
A A
AA
Johns Hopkins Asthma and Allergy Center, Department of Medicine, Baltimore, MD 21224.
Shinomiya
N
N
Zwollo
P
P
Marsh
D G
DG
D000485:Allergens; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D001483:Base Sequence; D006681:HLA-D Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010940:Plant Proteins; D011058:Pollen / Q000276:immunology*; D016133:Polymerase Chain Reaction
D000485:Allergens; D052179:Antigens, Plant; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; C062329:Lol p III protein, Lolium perenne; D010940:Plant Proteins