Human MHC class III and IV genes and disease associations

The major histocompatibility complex (MHC) was initially defined as the gen etic locus encoding the Class I and Class II highly polymorphic cell surfac e antigens that are now known to present antigen to matched sets of T cell receptors. Genes for several diverse complement components, specifically Bf , C2, and C4 were found between the Class I and II genes, in a region later dubbed Class III. More recently, several genes have been described that ar e encoded in the telomeric end of the Class III region and that appear to b e involved in both global and specific inflammatory responses. Due to this commonality of function this gene-rich region was dubbed Class IV, and incl udes the TNF family, AIF1, and HSP70. The genes of the Class III and Class IV regions are sufficiently divergent in sequence and structure so that clu stering is not explicable in terms of gene duplication or divergence. We pr esent some of the newer pertinent information and puzzling features of the genes embraced in the Class IV region and discuss possible roles in specifi c autoimmune diseases linked to this region.