Allo-HLA Cross-Reactivities of Cytomegalovirus-, Influenza-, and Varicella Zoster Virus-Specific Memory T Cells Are Shared by Different Healthy Individuals.
Virus-specific T cells can recognize allogeneic HLA (allo-HLA) through TCR cross-reactivity. The allospecificity often differs by individual (private cross-reactivity) but also can be shared by multiple individuals (public cross-reactivity); however, only a few examples of the latter have been described. Because these could facilitate alloreactivity prediction in transplantation, we aimed to identify novel public cross-reactivities of human virus-specific CD8+T cells directed against allo-HLA by assessing their reactivity in mixed-lymphocyte reactions. Further characterization was done by studying TCR usage with primer-based DNA sequencing, cytokine production with ELISAs, and cytotoxicity with51chromium-release assays. We identified three novel public allo-HLA cross-reactivities of human virus-specific CD8+T cells. CMV B35/IPS CD8+T cells cross-reacted with HLA-B51 and/or HLA-B58/B57 (23% of tetramer-positive individuals), FLU A2/GIL (influenza IMP[58-66] HLA-A*02:01/GILGFVFTL) CD8+T cells with HLA-B38 (90% of tetramer-positive individuals), and VZV A2/ALW (varicella zoster virus IE62[593-601] HLA-A*02:01/ALWALPHAA) CD8+T cells with HLA-B55 (two unrelated individuals). Cross-reactivity was tested against different cell types including endothelial and epithelial cells. All cross-reactive T cells expressed a memory phenotype, emphasizing the importance for transplantation. We conclude that public allo-HLA cross-reactivity of virus-specific memory T cells is not uncommon and may create novel opportunities for alloreactivity prediction and risk estimation in transplantation.
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
H
H
van den Heuvel
Department of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.|Renal Transplant Unit, Department of Internal Medicine, Division of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
K M
KM
Heutinck
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
E M W
EMW
van der Meer-Prins
Department of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.|Renal Transplant Unit, Department of Internal Medicine, Division of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
S L
SL
Yong
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
P P M C
PPMC
van Miert
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
J D H
JDH
Anholts
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
M E I
MEI
Franke-van Dijk
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
X Q
XQ
Zhang
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
D L
DL
Roelen
Renal Transplant Unit, Department of Internal Medicine, Division of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
R J M
RJM
Ten Berge
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
F H J
FHJ
Claas
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000821:virology; D006680:HLA Antigens / Q000276:immunology*; D064368:Healthy Volunteers; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007251:Influenza, Human / Q000821:virology; D009975:Orthomyxoviridae / Q000276:immunology*; D000073618:Varicella Zoster Virus Infection / Q000821:virology
D006680:HLA Antigens
alloantigen; antigen presentation/recognition; basic (laboratory) research/science; histocompatibility; immunobiology; immunogenetics; infection and infectious agents; major histocompatibility complex (MHC); organ transplantation in general; translational research/science; viral