A role for major histocompatibility complex (MHC) class II molecules in MHC class I presentation and CD8 T cell priming

The CD4 T cell response against hen egg lysozyme (HEL) in non‐obese diabetic (NOD) mice comprises a majority of T cells reactive against HEL 11–25 despite the presence of another epitope, HEL 20–35, that binds to A g7 with comparable affinity. To investigate further the relationship between peptide affinity and the T cell response, we used ELISPOT to measure cytokine production after priming with HEL. As expected, HEL immunization of NOD mice generated HEL 11–25‐reactive CD4 T cells that secreted interleukin‐2 (IL2) and interferon‐γ (IFNγ). Surprisingly, HEL immunization also gave rise to a robust CD8 T cell response specific for HEL 23–31 presented by D b . Another interesting aspect of these studies was the finding that mice expressing D b but lacking A g7 showed a reduced or absent CD8 T cell response after HEL immunization. A lack of CD4 T cell help could not explain this result, as depletion of CD4 T cells prior to immunization with HEL had a minimal effect on CD8 T cell priming. To test the global effect of MHC class II molecules on MHC class I peptide selection, we have initiated mass spectrometry studies on peptides bound to K d in the presence or absence of A g7 . Initial results indicate a substantial difference in the K d peptide repertoire between cell lines with and without A g7 expression. Altogether, these data suggest a cooperativity between MHC class I and II that affects T cell priming and peptide selection.