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 beta, A alpha, E alpha, and E beta 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 alpha and A beta 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 beta 1 domain of A beta to play a predominant role in such restricted antigen recognition. Preliminary data refining this analysis to sites within beta 1, as well as data on control of alpha: beta chain association, are reviewed, and future prospects for use of this approach in resolving questions of immunological interest are discussed.