"Exon-shuffling" maps control of antibody- and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A beta.

Publisher Website
Google Scholar
Abstract
To investigate the role of the highly polymorphic amino-terminal (.beta.1) domain of the class II major histocompatibility polypeptide A.beta. during recognition by T cells and antibodies, exon-shuffling was carried out between genomic recombinant DNA clones of .**GRAPHIC**. and .**GRAPHIC**. to generate a hybrid gene containing .**GRAPHIC**. exons for the amino-terminal domain followed by the .**GRAPHIC**. exons for the remainder of the molecule. L-cell gene transfectants expressing this hybrid A.beta. gene in combination with .**GRAPHIC**. were compared to L cells expressing wild-type .**GRAPHIC**. dimers in tests of antigen-presentation to T-cell clones and hybridomas and for staining by a panel of anti-I-Ak-specific monoclonal antibodies. These antibodies were also tested for their reactivity with a B-lymphoma transfectant expressing .**GRAPHIC**. in the absence of .**GRAPHIC**. The results showed no qualitative differences in either T-cell or antibody-mediated recognition of I-Ak molecules containing either the exon-shuffled or wild-type .**GRAPHIC**. Together with the data involving the B cell transfectant expressing only .**GRAPHIC**. These results map control of the A.beta. contribution to the immunologically relevant determinants of I-Ak to the highly polymorphic amino-terminal domain and indicate little, if any, contribution to allele-specific recognition by amino acid sequence variations in the remaining portions of the A.beta. polypeptide.