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Articles |
/β T Cells by the Class Ib Gene Product, Qa-1b
Division of Molecular and Clinical Rheumatology, Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205
T cell hybridomas isolated from nonresponder H-2b mice immunized with pork insulin were stimulated by insulin in the presence of major histocompatibility complex (MHC)-unmatched antigen presenting cells. The restriction element used by these CD4– T cells was mapped to an oligomorphic MHC class Ib protein encoded in the T region and identified as Qa-1b using transfectants. The antigenic determinant was localized to the insulin B chain, and experiments with truncated peptides suggested that it is unexpectedly long, comprising most or all of the 30 amino acid B chain. The antigen processing pathway used to present insulin to the Qa-1b– restricted T cells does not require transporters associated with antigen processing (TAP), and it is inhibited by chloroquine. A wide variety of cell lines from different tissues efficiently present soluble insulin to Qa-1b–restricted T cells, and insulin presentation is not enhanced by phagocytic stimuli. Our results demonstrate that Qa-1b 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.
Key Words: antigen processing • major histocompatibility proteins • class Ib molecules • T cells • insulin
Abbreviations used: β2m, β2-microglobulin; BFA, brefeldin A; ER, endoplasmic reticulum; Ii, class II invariant chain; IR, insulin receptor; Qdm, Qa-1 determinant modifier; SEB, staphylococcal enterotoxin B; TAP, transporters associated with antigen processing.
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