LINKAGE DISEQUILIBRIUM BETWEEN HLA CLASS-II (DR, DQ, DP) AND ANTIGEN-PROCESSING (LMP TAP, DM) GENES OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

TAP, LMP and DM genes map within the major histocompatibility complex (MHC) class II region between the DQB1 and DPB1 loci, and are involved in the processing of peptides bound to HLA class I or class II molecu les. In order to determine the various linkage disequilibria existing between these genes and HLA class II genes, we have analyzed TAP1, TAP 2, LMP2, DMA, DMB, DRB1, DQA1, DQB1 and DPB1 polymorphisms in 162 unre lated healthy Caucasian individuals. Many positive or negative associa tions were observed between alleles at these loci, such as between DR/ DQ and TAP2, DM or LMP, between DP and DMB, and between TAP2 and DM, T AP2 and LMP. Conversely, no Linkage disequilibrium was detected betwee n some closely related genes (DR/DQ and TAP1, TAP1 and TAP2, LMP2 and DM), in agreement with the existence of recombination hot spots in thi s region. Other weak linkage disequilibria are likely to exist in this region. These data allow to define some conserved MHC class II haplot ypes including HLA class II and TAP, LMP and DM alleles. Furthermore, the knowledge of such linkage disequilibria is of outstanding importan ce in order to avoid misinterpretation of the data when studying MHC c lass II associations with autoimmune diseases.