Murine MHC class Ib gene T11: a functional paralog of T23/Qa-1? (106.42)

Abstract

Abstract MHC class Ia molecules, H2-K/D/L in mouse, select CD8 T cells during development and present peptides to appropriate CD8 T cells in immune responses. Mouse MHC class Ib H2-Q, T, M regions contain more than 20 protein-encoding genes, but only few have been studied. Qa-1, encoded by H2-T23 gene, is one of the best-studied MHC class Ib. Qa-1 presents peptide generated from MHC Ia to NKG2A/CD94 receptors and provides inhibitory signal to NK cells. Here, we report the study of another MHC class Ib gene, H2-T11. T11 is 95% identical in DNA level and 87% identical in protein level to T23. T11 mRNA was detected in spleen, thymus and uterus in B6 mice, and its expression pattern is more limited than that of T23. Recombinant T11 was refolded with β2m, with or without the exogenous Qdm peptides. The refolded T11 had a typical secondary structure of MHC class I proteins, shown by circular dichroism analysis. The refolded T11 bound Qdm in vitro and could be recognized by a Qa-1 specific mAb. T11 was ectopically expressed on the surface of several cell lines, including a Tap deficient one. The T11 expressing cells could not present insulin to Qa-1 restricted, insulin-specific T cell hybridoma, in contrast to T23 expressing cells. Our results indicated that despite a high similarity to T23, T11 might have different function from T23/Qa-1. We are in the process of eluting naturally bound peptides from T11 expressing cells, and using T11/Qdm tetramers to look for its potential ligand(s).