Tap independent presentation of soluble insulin to αβ T cells by the class Ib gene product Qa-lb

MHC class Ib molecules are oligomorphic proteins which associate with β₂m. These "non-classical" MHC class I proteins have been shown to present peptides to both αβ and γδ T cells, possibly having a specialized role in antigen presentation and T cell activation. In general, MHC class I proteins present a sample of peptides derived from cytosolic antigens to T lymphocytes. Here we provide evidence of a unique exception: the presentation of soluble insulin by the MHC class Ib protein, Qa-lb to cloned T cell hybridomas. Two CD4-CD8- αβ T cell hybridomas (Pb-13 and Pb-20) from insulin primed H-2_b, low-responder mice, recognize a B chain epitope of insulin, presented in the context of Qa-lb. Most reports suggest only phagocytic cells can present soluble antigen associated with class I molecules. We find that B cells and L cell transfectants expressing Qa-lb can efficiently stimulate Pb-13 and Pb-20. While Qa-lb expression is required, it is not sufficient for presentation of insulin to Pb-13 or Pb20. Additionally, insulin loading of Qa-lb is independent of TAP transporter proteins, suggesting the use of a novel class I antigen processing pathway. We speculate that these T cells may be important in regulation of the immune response analogous to regulatory CTL specific for TCR-V-derived peptides presented by Qa-lb. Supported by NTH grant AI33614.