Human ir genes: Structure and function

The murine Ir region occupies a 0.2 cM region on the short arm of chromosome 17. Products of this region, termed “immune response associated” or “Ia molecules,” consist of a bimolecular complex that is noncovalently associated on the surface of B cells, macrophages, some T cells, dendritic cells, and Langerhan's cells. The structure of α chains from different strains of mice appears relatively constant, while the polymorphism among strains is carried on the β chains. The F₁ progeny of inbred strains of mice have I-A and I-E molecules representative of those present in each parent as well as new Ia molecules created by associations between α and β chains inherited from each parent. There is a third type of molecule detected in immunoprecipitations of murine Ia molecules, the invarient chain I_i. This glycoprotein is common to all Ia immunoprecipitates, has a molecular weight of 31,000, and appears to be associated with Ia antigens during their cytoplasmic processing. The best characterized human Ia molecule (HLA-DR) is a product of genes in the HLA-D region. During their development within the thymus, T cells contact Ia bearing stromal cells. This contact reflects a selection process that results in the emigration of only T cells that can recognize self Ia molecules in conjunction with other conventional antigen. The activation of peripheral T cells requires that they not only recognize determinants inherent in conventional antigen but also determinants inherent in Ia molecules displayed by antigen presenting cells. The functional studies indicate that HLA-DR and HLA-DS molecules can function as restriction elements that determine reactivity to simple antigens as well as immunodominant determinants present in complex antigens.