Qa-2 and Qa-1 are murine nonclassical MHC class I molecules involved in the modulation of immune responses by interacting with T CD8+and NK cell inhibitory receptors. During thymic education, theAiregene imposes the expression of thousands of tissue-related antigens in the thymic medulla, permitting the negative selection events. Aiming to characterize the transcriptional profiles of nonclassical MHC class I genes in spatial-temporal association with theAireexpression, we evaluated the gene expression ofH2-Q7(Qa-2),H2-T23(Qa-1),H2-Q10(Qa-10), andAireduring fetal and postnatal development of thymus and other tissues. In the thymus,H2-Q7(Qa-2) transcripts were detected at high levels throughout development and were positively correlated withAireexpression during fetal ages.H2-Q7(Qa-2) andH2-T23(Qa-1) showed distinct expression patterns with gradual increasing levels according to age in most tissues analyzed.H2-Q10(Qa-10) was preferentially expressed by the liver. TheAiretranscriptional profile showed increased levels during the fetal period and was detectable in postnatal ages in the thymus. Overall, nonclassical MHC class I genes started to be expressed early during the ontogeny. Their levels varied according to age, tissue, and mouse strain analyzed. This differential expression may contribute to the distinct patterns of mouse susceptibility/resistance to infectious and noninfectious disorders.