TRANSPORTERS ASSOCIATED WITH ANTIGEN-PROCESSING (TAP)-INDEPENDENT PRESENTATION OF SOLUBLE INSULIN TO ALPHA BETA-T CELLS BY THE CLASS IB GENE-PRODUCT, QA-1(B)/

T cell hybridomas isolated from nonresponder H-2(b) mice immunized wit h pork insulin were stimulated by insulin in the presence of major his tocompatibility complex (MHC)-unmatched antigen presenting cells. The restriction element used by these CD4(-) T cells was mapped to an olig omorphic MHC class Ib protein encoded in the T region and identified a s Qa-1(b) using transfectants. The antigenic determinant was localized to the insulin B chain, and experiments with truncated peptides sugge sted that it is unexpectedly long, comprising most or all of the 30 am ino acid B chain. The antigen processing pathway used to present insul in to the Qa-1(b)-restricted T cells does not require transporters ass ociated with antigen processing (TAP), and it is inhibited by chloroqu ine. A wide variety of cell lines from different tissues efficiently p resent soluble insulin to Qa-1(b)-restricted T cells, and insulin pres entation is not enhanced by phagocytic stimuli. Our results demonstrat e that Qa-1(b) can function to present exogenous protein to T cells in a manner similar to MHC class II molecules. Therefore, this class Ib protein may have access to a novel antigen processing pathway that is not available to class Ia molecules.