Suboptimal recognition of a T cell epitope of the major dog allergen Can f 1 by human T cells.
We have previously proposed that mammalian lipocalin allergens are recognized suboptimally by the human immune system due to their homology with endogenous lipocalins. Here, we have characterized in detail the human T cell recognition of one of the previously identified T cell epitopes of the major dog allergen Can f 1, contained in peptide p105-120. A panel of peptide analogues (altered peptide ligands, APLs) of p105-120 was tested on two specific T cell clones restricted by different human leukocyte antigen (HLA) alleles. Interestingly, we identified for both of the clones several heteroclitic APLs that were capable of stimulating them at 10-30-fold lower concentrations than the natural peptide. Moreover, one of the heteroclitic APLs identified with the T cell clones, L115F, was observed to induce a stronger polyclonal T cell response than the natural allergen peptide from the peripheral blood mononuclear cells (PBMCs) of six Can f 1-allergic subjects studied. The heteroclitic APLs bound with the same affinity as p105-120 to common HLA-DR- and HLA-DP-alleles, suggesting that their improved stimulatory capacity is attributable to a more efficient T cell receptor (TCR) recognition rather than increased HLA binding. Collectively, our data suggest that p105-120 is recognized suboptimally by human T cells. This may contribute to the allergenicity of Can f 1.
Juntunen
Riikka
R
Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Kuopio, Kuopio, Finland.
Liukko
Aino
A
Taivainen
Antti
A
Närvänen
Ale
A
Durand
Guillaume
G
Kauppinen
Anu
A
Nieminen
Anssi
A
Rytkönen-Nissinen
Marja
M
Saarelainen
Soili
S
Maillère
Bernard
B
Virtanen
Tuomas
T
Kinnunen
Tuure
T
D000483:Alleles; D000485:Allergens / Q000235:genetics / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006682:HLA-DP Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D054834:Lipocalins / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D054834:Lipocalins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C091462:allergen Can f I