Molecular analysis of the HLA-D region has uncovered a complex array of related genes encompassing a minimum of 6 alpha and 7 beta chain sequences. A high level of polymorphism is characteristic of the DQ alpha and beta genes, as well as DR beta. The DP genes, both alpha and beta, are also polymorphic, though to a lesser extent. The genes fit into the previously established loci: DP, DQ and DR, except for a newly-discovered sequence, DZ alpha, which is approximately equally related to all of the other alpha chain genes. Analysis of the polymorphism and evolution of the HLA-D region, by examination of the sequences, calls for several independent duplication events in the generation of this family of genes.

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Recent studies have identified a number of new genes mapping to the class-II region of the human major histocompatibility complex. Functionally these can be grouped into three broad categories: those encoding the new class-II-related genes DMA and DMB; those involved in aspects of class-I antigen-processing and presentation, and those with no apparent association with the immune system. There is evidence that further factors involved in class-II antigen presentation are located in the DMB to DQB1 interval.

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