The immunodominant epitope of lipocalin allergen Bos d 2 is suboptimal for human T cells.
We have proposed earlier that the poor capacity of the lipocalin allergen Bos d 2 to stimulate highly allergic subjects' peripheral blood mononuclear cells could be ascribed to endogenous lipocalins and could be related to the allergenic potential of the molecule. Here, we have characterized the proliferative and cytokine responses of human T cell clones against the immunodominant epitope of Bos d 2. We observed, for clone F1-9, that a substitution of aspartic acid for asparagine in the core region of the epitope increased the stimulatory capacity of the peptide about 100-fold in comparison with the natural peptide. For clone K3-2, from a different patient, the substitution of lysine for glutamine or isoleucine for leucine in the core region resulted in about 30-fold and 10-fold increases in the stimulatory capacity of the peptides, respectively. The clones also recognized self-protein-derived peptides but not the peptides derived from other lipocalins. We suggest that the poor recognition of the immunodominant epitope of Bos d 2 can be a factor accounting for Bos d 2-allergic subjects' weak cellular responses. Suboptimal recognition of self and allergen epitopes by T cells may be of significance for the allergenicity of proteins.
Kinnunen
Tuure
T
Department of Clinical Microbiology, University of Kuopio, Finland.
Buhot
Cecile
C
Närvänen
Ale
A
Rytkönen-Nissinen
Marja
M
Saarelainen
Soili
S
Pouvelle-Moratille
Sandra
S
Rautiainen
Jaakko
J
Taivainen
Antti
A
Maillère
Bernard
B
Mäntyjärvi
Rauno
R
Virtanen
Tuomas
T
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology; D052179:Antigens, Plant; D001249:Asthma / Q000209:etiology; D001324:Autoantigens / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D002417:Cattle / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D003429:Cross Reactions; D004391:Dust; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D059811:HLA-DRB1 Chains; D059845:HLA-DRB4 Chains; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011485:Protein Binding; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000485:Allergens; D015478:Antigens, Heterophile; D052179:Antigens, Plant; D001324:Autoantigens; C113339:Bos d 2 allergen; D002352:Carrier Proteins; D004391:Dust; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059845:HLA-DRB4 Chains; D016056:Immunodominant Epitopes; D010446:Peptide Fragments