Detailed characterization of human <italic>Mycobacterium tuberculosis</italic> specific HLA‐E restricted CD8+ T cells.

Abstract: HLA‐E presented antigens are interesting targets for vaccination given HLA‐Es’ essentially monomorphic nature. We have shown previously that <italic>Mycobacterium tuberculosis</italic> (Mtb) peptides are presented by HLA‐E to CD8⁺ effector T cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA‐E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb‐peptide/HLA‐E‐TM⁺ CD8⁺ T cells in the circulation of patients with active tuberculosis (TB). HLA‐E restricted CD8⁺ T cells from TB patients produced more IL‐13 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8⁺ T cells, HLA‐E restricted cells produced more IFNγ, IL‐4, IL‐10, and granulysin but less granzyme‐A. Moreover, compared to “classical” Mtb specific HLA‐A2 restricted CD8⁺ T cells, HLA‐E restricted CD8⁺ T cells produced less TNFα and perforin, but more IL‐4. In conclusion, HLA‐E restricted‐ Mtb specific cells can produce Th2 cytokines directly. [ABSTRACT FROM AUTHOR]