Nonconventional (TL-encoded) major histocompatibility complex molecules present processed viral antigen to cytotoxic T lymphocytes.

A large number of class I-like genes are located distal to the K and D regions of the murine major histocompatibility complex (MHC) within the Q and TL region. The function of the molecules encoded within this region is obscure since unlike conventional MHC gene products, these molecules have not been reported to present processed environmental antigens to T cells. In the present report, we demonstrate that a peptide corresponding to processed influenza virus hemagglutinin can be recognized by CD8+ T cell receptor alpha/beta-positive cytotoxic T lymphocytes (CTL) in association with a MHC class I-like product encoded within the TL region. Thus, nonconventional class I MHC molecules can bind and present processed environmental antigens, and TCR-alpha/beta CTL directed to such peptide MHC complexes are represented in the mature T cell pool. Our data imply that Q/TL region products may be charged by peptides generated through an antigen processing and presentation pathway distinct from the pathway used by conventional MHC molecules and not normally available to environmental antigens.