Use of molecular techniques for analysis of Ia structure-function relationships

An overview of a strategy for the molecular analysis of class II major histocompatibility complex (Ia) gene product structure-function relationships is presented, and results obtained to date by using this approach are summarized. The A(β), A(α), E(α), and E(β) genes have been cloned and sequenced to yield information on gene organization and primary protein sequence. Comparison of sequences from allelic forms of these genes show the NH₂-terminal domain to be the locus of most intraspecies polymorphism. Transfection of I-A(α) and A(β) genes into B lymphoma cells or L cells has generated cells expressing the transfected gene products on their membrane. Such Ia⁺ transfectants present antigen to various T cells, which use the expressed I-A as a restriction element. Exon shuffling has shown the β₁ domain of A(β) to play a predominant role in such restricted antigen recognition. Preliminary data refining this analysis to sites within β₁, as well as data on control of α:β chain association, are reviewed, and future prospects for use of this approach in resolving questions of immunological interest are discussed.