Infection with a virus generates a polyclonal immune response with broad alloreactive potential

Area of Science:

• Immunology
• Transplantation Immunology
• Viral Immunology

Background:

• Virus-specific T cells exhibit cross-reactivity with allogeneic HLA (allo-HLA) at a clonal level.
• The polyclonal impact of a single virus on the allorepertoire remains uninvestigated.

Purpose of the Study:

• To inventory the incidence and specificity of allo-HLA-cross-reactive virus-specific CD8+ T cells in healthy individuals.
• To determine if a single virus can broaden the allo-HLA memory T-cell repertoire at a polyclonal level.

Main Methods:

• Inventory of allo-HLA-cross-reactive virus-specific CD8+ T cells in 24 healthy individuals.
• T-cell staining for 25 virus-specific tetramers and mixed-lymphocyte reactions against HLA-typed allostimulators.
• Confirmation of allospecificity via IFNγ-ELISA using T-cell clones against HLA-typed cell-lines.

Main Results:

• The polyclonal immune repertoire against Cytomegalovirus (CMV) alone was linked to memory responses against six allo-HLA molecules.
• A single allostimulator triggered memory T-cell responses with diverse viral specificities.
• A single virus substantially broadens the allo-HLA memory T-cell repertoire.

Conclusions:

• A single viral infection can significantly expand the polyclonal allo-HLA memory T-cell repertoire.
• Transplant patients with HLA-mismatched grafts may possess a pre-existing polyclonal repertoire of anti-donor memory T cells.
• Further research is needed to explore the impact of T cells against various viruses on the immune repertoire.