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Variable Immunodominance Hierarchies for H2-M3-Restricted N-Formyl Peptides Following Bacterial Infection¹

Sections of Infectious Diseases and Immunobiology, Yale University School of Medicine, New Haven, CT 06520

H2-M3-restricted presentation of N-formyl methionine (f-Met) peptides to CD8⁺ T cells provides a mechanism for selective recognition of bacterial infection. In this report we demonstrate that Listeria monocytogenes infection induces distinct CD8⁺ T cell populations specific for each of the known Listeria-derived formyl methionine peptides presented by M3. The sum H2-M3-restricted, Listeria-specific T cell response constitutes a major fraction of the total CD8⁺ T cell response to primary infection. H2-M3-restricted T cell populations expand synchronously in vivo and achieve peak frequencies 2 days earlier than MHC class Ia-restricted T cell populations. Although cross-recognition of different f-Met peptides by M3-restricted T cells was previously described, costaining of CD8⁺ T cells ex vivo with H2-M3 tetramers complexed with different f-Met peptides shows that the majority of Listeria-specific, M3-restricted CD8⁺ T cells are peptide specific. In contrast to the highly predictable size and immunodominance hierarchies of MHC class Ia-restricted T cell responses, the magnitudes of T cell responses specific for H2-M3-restricted peptides are remarkably variable between genetically identical mice. Our findings demonstrate that H2-M3-restricted T cell responses are distinct from classically restricted T cell responses to bacterial infection.

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