ORGANIZATION AND FUNCTIONS OF CLASS-II GENES AND MOLECULES

The class II region of the human MHC contains all of the known class I I genes: as well as antigen processing components and only one gene no t obviously associated with the immune system, RING3. As an approach t o understanding Linkage disequilibrium and recombination in relation t o polymorphism of the region we are cloning and sequencing the class L I region. To date, the sequence of the DP-DQ region has almost been co mpleted (see Report by S. Beck). Several sets of genes implicated in t he immune system, especially in antigen processing and presentation, a re clustered together in the MHC: class I (HLA-A, B, C etc) class II ( DR, DQ, DP, DN, DO, DM) LMP2 and 7, TAP1 and 2, TNF, C2, C4, Bf, Hsp70 . This situation has provoked speculation that the MHC behaves as a ge ne cluster in which allelic products of polymorphic genes are maintain ed on a haplotype so as to co-ordinate T cell repertoire development a nd deployment. The high levels of linkage disequilibrium across the re gion are consistent with this idea. Functions of the genes in the MHC are being investigated as a step towards gaining insight into antigen processing and presentation as well as understanding MHC-disease assoc iations. We are concentrating on the functions of the class II-related genes, DM and DN/DO as well as the TAP/LMP cluster.