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Epitope affinity for MHC class I determines helper requirement for CTL priming

Abstract

We show here that priming and memory generation of antigen-specific CD8+ cytotoxic T lymphocytes (CTL) does not require help if the immunogen binds major histocompatibility complex (MHC) class I molecules with high affinity. This conclusion was based on the study of three chemically distinct optimal length CTL epitopes with high affinity for the restriction element Kb. In contrast, when two subdominant epitopes with intermediate MHC binding affinity were studied, either a class II MHC–restricted T helper cell epitope or administration of antibody to CD40 was required to obtain significant CTL priming. Depending on the epitope, one source of help was much more efficient than the other.

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Figure 1: CTL response generated in the absence of help.
Figure 2: CTL induction in MHC class II–deficient mice.
Figure 3: CTL induction dependency on help with antigens of lower Kb binding affinity.
Figure 4: Memory CTL response.

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Acknowledgements

We thank V. Barnaba and G. Ishioka for discussions, S. Schoenberger for mAb to CD40, A. Sette and J. Sidney for Kb binding analysis of the two subdominant epitopes, M.R. Ullah for peptide synthesis, Y. Wang-Zhu for the CTLL-2 cell line, D. O'Masters for animal care assistance and J. Joseph for assistance in manuscript preparation. Supported by grants from the National Institutes of Health (to A.F. and H.G.). This is manuscript no.369 from the La Jolla Institute for Allergy and Immunology.

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Franco, A., Tilly, D., Gramaglia, I. et al. Epitope affinity for MHC class I determines helper requirement for CTL priming. Nat Immunol 1, 145–150 (2000). https://doi.org/10.1038/77827

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