Background: Diisocyanates are the most common cause of occupational asthma induced by low-molecular-weight chemicals. The disease appears to be immunologically mediated but is independent of IgE antibody synthesis. An underlying genetic susceptibility is suggested by the fact that the disease only develops in approximately 5% to 10% of exposed workers. Objective: The study was designed to determine whether disease susceptibility is influenced by HLA and T-cell receptor Vβ gene segment usage. Methods: T-cell receptor Vβ gene repertoires were quantitated by using primer pairs specific for Vβ gene segments in conjunction with a common Cβ region primer. One group of workers with diisocyanate-induced occupational asthma produced diisocyanate-specific IgG and IgE antibodies, whereas the other group did not produce specific antibodies. Occupational asthma was previously confirmed by either workplace challenge or laboratory specific diisocyanate bronchoprovocation. Control groups consisted of diisocyanate-exposed workers who were free of symptoms, patients with nonoccupational asthma, and unexposed subjects who were free of symptoms. Results: Lymphocytes from workers with diisocyanate-induced occupational asthma had significantly decreased Vβ1 and Vβ5 gene segment expression before in vitro exposure to diisocyanates, compared with control groups. Percent Vβ1 and Vβ5 gene segment expression was selectively increased when peripheral blood mononuclear cells were stimulated in vitro with diisocyanate-conjugated proteins. Low-resolution HLA class II phenotyping revealed no significant differences in the distribution of HLA-DR or HLA-DQ alleles between diisocyanate-induced occupational asthma and control groups. Conclusions: These findings are consistent with a hypothesis that antigen-specific T-cell subpopulations may be sequestered in the lungs of workers with diisocyanate-induced occupational asthma and clonally expand after further exposure to diisocyanates. (J Allergy Clin Immunol 1997;99:245-50.)