PMID- 19700193 OWN - NLM STAT- MEDLINE DCOM- 20091020 LR - 20101118 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 46 IP - 16 DP - 2009 Oct TI - Suboptimal recognition of a T cell epitope of the major dog allergen Can f 1 by human T cells. PG - 3320-7 LID - 10.1016/j.molimm.2009.07.022 [doi] AB - 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. FAU - Juntunen, Riikka AU - Juntunen R AD - Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Kuopio, Kuopio, Finland. FAU - Liukko, Aino AU - Liukko A FAU - Taivainen, Antti AU - Taivainen A FAU - Narvanen, Ale AU - Narvanen A FAU - Durand, Guillaume AU - Durand G FAU - Kauppinen, Anu AU - Kauppinen A FAU - Nieminen, Anssi AU - Nieminen A FAU - Rytkonen-Nissinen, Marja AU - Rytkonen-Nissinen M FAU - Saarelainen, Soili AU - Saarelainen S FAU - Maillere, Bernard AU - Maillere B FAU - Virtanen, Tuomas AU - Virtanen T FAU - Kinnunen, Tuure AU - Kinnunen T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090822 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Allergens) RN - 0 (Antigens, Plant) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-DP Antigens) RN - 0 (HLA-DR Antigens) RN - 0 (Lipocalins) RN - 0 (Peptides) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (allergen Can f I) SB - IM MH - Alleles MH - Allergens/genetics/*immunology MH - Animals MH - Antigens, Plant MH - Cells, Cultured MH - Dogs MH - Dose-Response Relationship, Drug MH - Epitopes, T-Lymphocyte/genetics/*immunology MH - HLA-DP Antigens/genetics/immunology MH - HLA-DR Antigens/genetics/immunology MH - Humans MH - Hypersensitivity/genetics/*immunology MH - Lipocalins/genetics/immunology MH - Peptides/genetics/*immunology/pharmacology MH - Receptors, Antigen, T-Cell/genetics/*immunology MH - T-Lymphocytes/*immunology EDAT- 2009/08/25 09:00 MHDA- 2009/10/21 06:00 CRDT- 2009/08/25 09:00 PHST- 2009/06/25 00:00 [received] PHST- 2009/07/26 00:00 [accepted] PHST- 2009/08/25 09:00 [entrez] PHST- 2009/08/25 09:00 [pubmed] PHST- 2009/10/21 06:00 [medline] AID - S0161-5890(09)00623-3 [pii] AID - 10.1016/j.molimm.2009.07.022 [doi] PST - ppublish SO - Mol Immunol. 2009 Oct;46(16):3320-7. doi: 10.1016/j.molimm.2009.07.022. Epub 2009 Aug 22.