Convergent clonal selection of donor- and recipient-derived CMV-specific T cells in hematopoietic stem cell transplant patients

Author:

Erickson Jami R.12ORCID,Stevens-Ayers Terry1,Mair Florian1ORCID,Edmison Bradley1,Boeckh Michael134ORCID,Bradley Philip5ORCID,Prlic Martin12

Affiliation:

1. Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109

2. Department of Global Health, University of Washington, Seattle, WA 98195

3. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109

4. Department of Medicine, Division of Allergy & Infectious Diseases, University of Washington, Seattle, WA 98195

5. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109

Abstract

Significance An existing memory T cell population specific for a single epitope is sufficient to effectively curtail responses to any new antigens if the original epitope is present in a vaccination regimen or heterologous infections. We asked if T cell competition precludes recruitment of any new, naïve T cells to an existing memory T cell pool in context of cytomegalovirus-specific T cell responses in a cohort of transplant patients. Our data indicate that competition does not prevent recruitment of naïve T cells into the memory T cell pool but selects for T cells with nearly or fully congruent T cell receptor specificities. We discuss the implications of rejuvenating a memory T cell pool while preserving the T cell receptor repertoire.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

HHS | NIH | NIH Office of the Director

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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