John L. Ohman

Definition of the human T-cell epitopes of Fel d 1, the major allergen of the domestic cat

BACKGROUND A heterodimeric acidic glycoprotein (Fel d 1) has been defined as the major allergen of the domestic cat. Because T-cell help is required for the initiation and maintenance of allergic responses, it is of importance to determine the T-cell-reactive regions of the Fel d 1 molecule. METHODS Overlapping peptides corresponding to the two chains of Fel d 1 were tested in proliferation assays on polyclonal T-cell lines and for the ability to bind Fel d 1-specific IgE in ELISA and histamine release assays. RESULTS Assay of T-cell lines derived from 53 subjects allergic to cats demonstrated that the majority of T-cell reactivity is found in chain 1 of Fel d 1. Two peptides (Fel-1 and Fel-2) containing major epitopes, alone or as a mixture, efficiently activated T cells and exhibited minimal detectable reactivity with IgE by ELISA or histamine release assay. CONCLUSIONS Two Fel d 1 peptides containing major T-cell epitopes have been identified, have been shown to bind minimal Fel d 1-specific IgE, and are now being tested for the ability to decrease T-cell responses in patients with cat allergy as a new form of immunotherapy.

Recommendations for the use of residential air-cleaning devices in the treatment of allergic respiratory diseases

In an attempt to recommend standards for room air-cleaning devices, a committee reviewed (1) the types and performance characteristics of available domestic air-cleaning devices, (2) the available data on concentrations of allergens in the indoor air, and (3) the studies that have examined the health effects of the use of indoor air-cleaning devices. Absense of adequate data on the clinical relevance of indoor ambient allergen levels, as well as the effect of air-cleaning devices on these levels, plus a general lack of health effects by these devices in published double-blind studies precluded any firm recommendations for their use. It was clear, however, that use of room air-cleaning devices in the absence of other forms of environmental control was not reasonable.

A comparative study of the allergens of cat urine, serum, saliva, and pelt

In direct RAST analyses of sera from 43 individuals with a history of cat allergy, 39.5% were positive to cat pelt, 37.5% to cat saliva, and 12% each to cat urine and serum. The cat pelt and saliva extracts contained allergen 1, but cat serum and cat urine collected by bladder puncture had no detectable levels of this allergen. A crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis analysis failed to reveal any allergen in urine or serum that was not also present in the saliva or pelt preparations, although urine had two allergens not present in serum. When serum from a patient who was direct RAST positive to cat pelt, serum, saliva, and urine was tested by crossed radioimmunoelectrophoresis, it was determined that a total of six allergens were detectable in cat pelt, three in cat urine, and six in cat serum. Since cat serum contains no detectable cat allergen 1, it may be concluded that at least seven allergens derived from the cat are capable of binding to IgE antibody in humans.

New onset wheezing in an older male population: Evidence of allergen sensitization in a longitudinal study: Results of the normative aging study

BACKGROUND Thirty-nine male subjects, with new-onset wheezing, were selected from participants in the Department of Veterans Affairs Normative Aging Study and compared with 74 age-matched controls. Wheezing was defined by responses to a standardized and regularly administered questionnaire. The subjects with wheezing had a reduced FEV1 compared with controls (p = 0.005), but most had values above 80% predicted. Current smoking was more common in subjects with wheezing (36.8% vs 8.11% in controls, p < 0.001). The mean age of both subjects and controls was 64 years. METHODS Allergen-specific IgE antibodies were measured, starting with sera at the time of the most recent questionnaire, and on the average 3.1, 7.6, and 12.3 years before that, with use of stored serum samples. RESULTS Total IgE did not differ significantly between the groups. IgE binding to dust mite antigen was detected in 13% to 15% of the subjects with wheezing compared with fewer than 7% of the controls over four time intervals (p = 0.014). IgE binding to cat and ragweed antigens did not differ significantly between groups. If current nonsmokers were analyzed separately, IgE binding to cat allergen was also slightly greater in subjects with wheezing compared with controls (p = 0.054). Sequential analysis of IgE antibody levels to mite antigen, over time, indicated that IgE antibody antedated the onset of wheezing. CONCLUSIONS New-onset wheezing in an older adult male population is significantly associated with allergic sensitization to dust mite. There was a borderline association with sensitization to cat in noncurrent smokers only. This supports the hypothesis that a subgroup may have allergic triggers to their symptoms.

Allergen-specific human T cell clones: derivation, specificity, and activation requirements

The interaction between allergen and immune cells plays a pivotal role in the development of human allergy. In an attempt to understand this interaction, we have studied allergen-specific T cells in vitro. These T cells are derived from rodent-allergic individuals and are specific for a major allergen found in mouse urine (MA-1). Antigen-specific, major histocompatibility complex-restricted, human T cell clones have been generated by limiting dilution from lines derived from the peripheral blood T cells of allergic individuals. Antigen (Ag)-presenting cells are necessary for this response, and they can be modulated by appropriate agents. These clones can be propagated in vitro under conditions of restimulation with Ag in the presence of Ag-presenting cells without the continuous use of exogenous interleukin-2. Most clones are CD3+ or CD4+, but one clone is CD3+ CD8+ by fluorescence-activated cell sorter and monoclonal antibody-killing data. Ag stimulation of these clones induces them to produce interleukin-2 and proliferate. These T cell clones can provide a basis for studying the structure of allergenic epitopes and the potential role of altered Ag in the induction of T cell tolerance. If the determinants of T cell allergen recognition and tolerance are solved, it might provide a basis for a new approach to the immunotherapy of allergic disease.