Immune-mediated diseases are among the strongest selective pressures driving human evolution. The major histocompatibility complex (MHC) locus that encodes human leukocyte antigen (HLA) proteins plays a vital role in our adaptive immune responses, and thus is crucial in understanding the human evolutionary process. Several non-competing natural selective regimes exist to explain how the MHC locus evolved, including balancing, and pathogen-driven positive and negative selection. However, owing to the complicated genomic structure of the MHC locus, it remains challenging to nominate specific genomic variations and haplotypes driving the observed selection signatures. In this talk, we will characterize HLA diversity among Gambian, China, Latino American and African American individuals. We will clarify selection dynamics that shaped the MHC locus in HLA selection signals.