In this article, the author discusses association of antileucine- rich glioma-inactivated1 (anti-LGI1) encephalitis with the major histocompatibility complex (MHC) II haplotype human leukocyte antigen (HLA). Topics discussed include observation of human leukocyte antigen (HLA) in several human immunemediated disorders; expression of MHC II on all nucleated cells; and therapeutic interventions in patients with anti-LGI1 encephalitis.