Genetic organization of the H2 class II region

The region of the mouse H2 complex containing the class II genes was historically called the T region, as it contains the aforementioned Ir genes, and the molecules encoded by these genes are called la antigens. The two classical class II antigens produced by the H2 complex are I-A and I-E. A current map of the class II region is shown in Figure 1. In addition to the genes which encode known functional class II molecules (Ap, Aa, Ep and Ea), there are four additional class II genes (Pb, Oa, Ob and Ep2) whose function is not yet clear. Although Pb appears to be a pseudogene, transcripts from the Oa, Ob and E(32 genes have been found. The Oa and Ob genes produce a nonpolymorphic, serologically recognized molecule with an expression pattern distinct from that of the classical H2 A and E molecules. That is, the H2 O molecules are expressed in spleen and

Ma Mb1 Pb Oa I Mb2 I

Ma Mb1 Pb Oa I Mb2 I

Figure 1 Genetic organization of the H2 class II region. Genes of known function are represented by filled rectangles.

lymph node follicles, but only in B cell-rich areas, suggesting H2 O is not expressed by macrophages and dendritic cells. H2 O is also found in thymus, but restricted to a population of medullary epithelial cells which arc virtually negative for H2 A and 1 expression. However, the functional role of the H2 O molecule remains elusive. The region between the Oa and Ob genes contains genes which encode prote-asomal subunits (LMP1 and LMP2), the peptide transporters for class I molecules (TAI'l and TAP2), and the three H2M genes whose products are involved in proper association of class II with antigenic peptides (Ma, Mbl and Mb2).

One of the great advantages which the mouse as an experimental animal has provided to the study of the structure and function of the MHC is the availability of a wide vareity of H2 recombinant mouse strains. Over 60 such strains were made by several laboratories and quickly made available to the scientific community. Knowledge of the MHC complexes of other organisms has not been achieved as rapidly due to the paucity of such intra-MHC recombinants. The study of H2 recombinants in the I region has revealed a 'hot spot' for recombination events within part of a large intron between exons 2 and 3 of the Ep gene. Comparisons of intra-MHC recombinant strains show a much higher degree of polymorphism to the left of this hot spot, i.e., from the 5' end of Ep through the Aa and Ap genes.

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