| Description |
Major histocompatibility complex (MHC) class Ib molecules share similar structure with the classical MHC class Ia molecules, but they generally have low expression levels and limited tissue distributions. Nevertheless, there are many different class Ib molecules and the well-studied ones have various specific functions. Many Ib molecules remain to be studied. Increasing evidence shows that MHC class Ib molecules can restrict CD8+ T cell responses during infections, just as the classical MHC class Ia molecules do. In this thesis, classical MHC class I deficient mice were employed to study the MHC class Ib restricted anti-lymphocytic choriomeningitis virus (LCMV) responses. The mice were able to generate CD8+ T cell dependent immune response to the acute viral infection and partially control the infection in the early phase. IFN! and granzyme B were produced in vivo by the CD8+ T cells. The response was restricted by MHC class Ib molecules as indicated by in vitro restimulation assays. However, the mounted responses were not strong enough to fully control the viral infection such that the infection becomes chronic in these mice and antigen-specific CD8+ T cells gradually lost their ability to produce cytokines and survive. One MHC class Ib molecule, H2-T11, was selected to test an approach for studying MHC class Ib systematically. H2-T11 has high similarity to the Qa-1b encoding gene, H2-T23. Reverse-transcriptional PCR and quantitative-PCR showed that it was expressed at relatively high levels in mouse spleen, thymus, and intestine. The transduced hybrid T11 molecule containing an antibody-recognizable H2-Db "3 domain could be detected on both TAP+/+ Hela and TAP-/- T2 cell surfaces. The hybrid T11 expressing cells were not able to present insulin to the 6C5 T cell hybridoma, while the hybrid T23 expressing cells did. While T23 required Qdm peptide for its in vitro folding, T11 could fold in the absence of Qdm peptides. However, in the presence of Qdm, the folding efficiency was higher. Multiple peptides were eluted from the hybrid T11 and T23 expressing Hela cells. Qdm was found in both T11 and T23 peptide pools, but it was much more frequently found from T23 pool. Fewer peptides were eluted from T11 than T23. The T11-Qdm tetramers could not recognize NK or NKT cells, but the T23-Qdm tetramers could. Together, these studies indicated that T11 might be a functional paralog to H2-T23, but it does not appear to share the specific functions of T23. |
