In human asthma the involvement of iNKT cells is still controversial, while there has been little analysis of MAIT cells. Using samples from the URban Environment and Childhood Asthma (URECA) birth cohort study, we carried out a comprehensive analysis of iNKT cells, MAIT cells and mainstream CD4⁺ T cells from the peripheral blood, and of the iNKT cell antigenic activity in house dust samples. These values were correlated with clinical outcomes, including aeroallergen sensitization and recurrent wheeze at 3 and asthma at age 7. Our results indicate that the iNKT cell frequency in the blood at one year of age was not correlated with the development of allergic sensitization or asthma. However, an increased content of iNKT cell antigens in the house dust was associated with protection from asthma. Furthermore, the frequency of MAIT cells was associated with increased production of IFNg by activated CD4⁺ T cells from children that did not go on to develop asthma. Moreover, an increased MAIT cell frequency early in life was associated with a decreased risk of asthma. Together, these data suggest that MAIT cell frequency and iNKT cell antigen exposure early in life correlates with protection from asthma development.