Human Lymphocyte Associated Antigen-1 (LFA-1, CD11a/CD18, alpha L/beta 2) and p150,95 (CD11c/CD18, alpha X/beta 2) are cell surface alpha/beta heterodimers that, together with Mac-1 (CD11b/CD18, alpha M/beta 2) comprise the leukocyte-restricted beta 2 subfamily of integrins. LFA-1 is the only integrin expressed on all leukocyte lineages while p150,95 is exclusively expressed on cells of the myeloid lineage and on activated B lymphocytes and natural killer cells. The expression of the leukocyte integrins is regulated during cell activation and differentiation by transcriptional mechanisms. To dissect the molecular basis for the tissue-restricted and developmentally regulated expression of LFA-1 and p150,95, the promoter regions of their corresponding alpha subunits (CD11a and CD11c) were isolated and functionally characterized. Both promoters lack TATA and CAAT boxes, but exhibit initiator-like sequences at their major transcriptional start sites. Transient expression of CD11a- and CD11c-based reporter gene constructs have demonstrated the involvement of both promoters in the tissue-specific expression of LFA-1 and p150,95. Furthermore, a combination of DNAse I protection experiments and mobility band shift assays have revealed the existence of numerous DNA-protein interactions at the proximal region of both promoters, some of which overlap with consensus binding sequences for known transcription factors and correlate with the pattern of expression of both integrins.