The MHC genes, haplotypes, and polymorphic molecules are investigated continuously due to their crucial role in the regulation of innate and adaptive immune responses; the pathogenesis of numerous infectious and/or autoimmune diseases; brain development and plasticity; olfaction; therapeutic vaccinations and T cell-based immunotherapy; and the compatibility of grafted tissue, which also concerns potential graft-versus-host disease involving hematopoietic stem cell transplants. Recent reports describe a role for neuronal MHC-I in synaptic plasticity, brain development, axonal regeneration, neuroinflammatory processes, and immune-mediated neurodegeneration. In humans, the MHC (HLA) genes are part of the supra-locus on chromosome 6p21 known as the human leukocyte antigen (HLA) system. This genomic complex consists of more than 200 genes, some located closely together as haplotype blocks and involved in inflammatory and immune-response, heat shock, and complement cascade systems; cytokine signalling; and the regulation of various aspects of cellular development, differentiation, and apoptosis. Also, there are thousands of putative microRNA encoding loci within HLA genes and the HLA genomic region that may be expressed by different cell types and play a role in the regulation of immune-response genes and in the etiology of numerous diseases.

The aim of this Special Issue is to examine further the role of the polymorphic MHC class I and class II genes, haplotypes, and molecules in health and disease in humans and other species in particular with respect to cellular functions. Analysing the structure, function, and disease associations of the MHC class I and class II genes and molecules in human and other species will improve our understanding of their role in innate and adaptive immunity, neurology and brain disease, autoimmunity, infectious diseases, cancer, and self and non-self recognition.