Background: Cry j 1 and Cry j 2 are thought to be the major allergens of Japanese cedar pollen. HLA class II types capable of presenting T–cell epitopes in both allergens and their role in induction of T–cell subsets are not well known. Methods: CD4+ T (Th)–cell clones (TCCs) specific to either Cry j 1 or Cry j 2 were generated. HLA class II restrictions were determined by their reactivity to the T–cell epitope in the presence of antigen presenting cells sharing matched types. Interleukin (IL)–2, interferon–γ, IL–4, and IL–5 contents in the supernatants of TCCs were estimated using enzyme immunoassay. Results: Peripheral blood mononuclear cells (PBMC) from patients induced proliferation with 100 μg/ml Cry j 1 or 3–10 μg/ml rCry j 2 stimulation. T–cell epitopes in Cry j 1 were presented to Th cells by the gene products of DRA1*01/DRB1*0901, DRA1*01/DRB5*0101, DQA1* 0102/DQB1*0602, and DPA1*01/DPB1*0501; those in Cry j 2 were restricted by DRA1*01/DRB1*0901, DRA1* 01/DRB1*1501, DRA1*01/DRB4*01, DRA1*01/DRB5* 0101, DQA1*0102/DQB1*0602, DPA1*01/DPB1*0201, and DPA1*01 and *0202/DPB1*0501. Type 2–like cells were preferentially induced in Cry j 1 stimulation, while an almost equal number of type 2– and type 1–like cells was induced in rCry j 2. Conclusions: No clear correlation existed between peptide specificity, HLA class II restriction and induction of Th–cell subsets, suggesting that the requirement of different dose of Cry j 1 or Cry j 2 to induce proliferation in PBMC may lead to distinguishable difference in induction of Th subsets between TCCs specific to Cry j 1 and Cry j 2.