Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions.
Intradermal administration of short overlapping peptides derived from chain 1 of the cat allergen Fel d 1 (FC1P) that did not cross-link IgE, elicited isolated late asthmatic reactions with no visible early or late cutaneous response in 9/40 cat-allergic asthmatics. Four of the nine were human histocompatibility leukocyte antigen DR13-positive, as compared with only 1/31 nonreactors. The other five reactors expressed either DR1 or DR4. To confirm major histocompatibility complex restriction, fibroblast cell lines transfected with HLA-DR molecules were used to present FC1Ps to cat allergen-specific T cell lines derived from subjects before peptide injection. FC1P3 (peptide 28-44 of Fel d 1 chain 1) was recognized in the context of DR13 alleles (DRB1*1301, 1302) and induced specific T cell proliferation and IL-5 production. T cells from a DR1(+) responder proliferated and produced IL-5 in the presence of FC1P3 and DR1 (DRB1*0101) fibroblast cell lines, whereas T cells from a DR4(+) subject recognized FC1P2 (peptide 22-37) when presented by DRB1*0405. We conclude that short, allergen-derived peptides can directly initiate a major histocompatibility complex-restricted, T cell-dependent late asthmatic reaction, without the requirement for an early IgE/mast cell-dependent response, in sensitized asthmatic subjects.
Haselden
B M
BM
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College School of Medicine, London SW3 6LY, United Kingdom.
Kay
A B
AB
Larché
M
M
D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology*; D001491:Basophils / Q000276:immunology; D002415:Cats; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage*; D006684:HLA-DR Antigens / Q000032:analysis; D006632:Histamine / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007271:Injections, Intradermal; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology
D000485:Allergens; D006023:Glycoproteins; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D014373:Tuberculin; D007073:Immunoglobulin E; D006632:Histamine; C059296:Fel d 1 protein, Felis domesticus