Sorbonne Université, INSERM, Immunology‐Immunopathology‐Immunotherapy, Paris, France; AP‐HP, Hôpital Pitié‐Salpêtrière, Clinical Investigation Center for Biotherapies (CIC‐BTi) and Immunology‐Inflammation‐Infectiology and Dermatology Department (3iD), Paris, France
Pierre Barennes
Sorbonne Université, INSERM, Immunology‐Immunopathology‐Immunotherapy, Paris, France; AP‐HP, Hôpital Pitié‐Salpêtrière, Clinical Investigation Center for Biotherapies (CIC‐BTi) and Immunology‐Inflammation‐Infectiology and Dermatology Department (3iD), Paris, France
Sorbonne Université, INSERM, Immunology‐Immunopathology‐Immunotherapy, Paris, France; AP‐HP, Hôpital Pitié‐Salpêtrière, Clinical Investigation Center for Biotherapies (CIC‐BTi) and Immunology‐Inflammation‐Infectiology and Dermatology Department (3iD), Paris, France
Paul Stys
Sorbonne Université, INSERM, Immunology‐Immunopathology‐Immunotherapy, Paris, France
Helene Vantomme
Sorbonne Université, INSERM, Immunology‐Immunopathology‐Immunotherapy, Paris, France; AP‐HP, Hôpital Pitié‐Salpêtrière, Clinical Investigation Center for Biotherapies (CIC‐BTi) and Immunology‐Inflammation‐Infectiology and Dermatology Department (3iD), Paris, France
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France
Federica Martina
AP‐HP, Hôpital Pitié‐Salpêtrière, Clinical Investigation Center for Biotherapies (CIC‐BTi) and Immunology‐Inflammation‐Infectiology and Dermatology Department (3iD), Paris, France
Nicolas Coatnoan
AP‐HP, Hôpital Pitié‐Salpêtrière, Clinical Investigation Center for Biotherapies (CIC‐BTi) and Immunology‐Inflammation‐Infectiology and Dermatology Department (3iD), Paris, France
Michele Barbie
AP‐HP, Hôpital Pitié‐Salpêtrière, Clinical Investigation Center for Biotherapies (CIC‐BTi) and Immunology‐Inflammation‐Infectiology and Dermatology Department (3iD), Paris, France
Hang-Phuong Pham
ILTOO pharma, Statistical department, Paris, France
Béatrice Clémenceau
CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France
Henri Vie
CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France
Center of Life Sciences, Skoltech, Moscow, Russian Federation
Adrien Six
Sorbonne Université, INSERM, Immunology‐Immunopathology‐Immunotherapy, Paris, France
Barbara Brandao
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France
Roberto Mallone
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France; Assistance Publique Hôpitaux de Paris, Service de Diabétologie et Immunologie Clinique, Cochin Hospital, Paris, France
Encarnita Mariotti-Ferrandiz
Sorbonne Université, INSERM, Immunology‐Immunopathology‐Immunotherapy, Paris, France
Sorbonne Université, INSERM, Immunology‐Immunopathology‐Immunotherapy, Paris, France; AP‐HP, Hôpital Pitié‐Salpêtrière, Clinical Investigation Center for Biotherapies (CIC‐BTi) and Immunology‐Inflammation‐Infectiology and Dermatology Department (3iD), Paris, France
T-cell receptors (TCRs) are formed by stochastic gene rearrangements, theoretically generating >1019 sequences. They are selected during thymopoiesis, which releases a repertoire of about 108 unique TCRs per individual. How evolution shaped a process that produces TCRs that can effectively handle a countless and evolving set of infectious agents is a central question of immunology. The paradigm is that a diverse enough repertoire of TCRs should always provide a proper, though rare, specificity for any given need. Expansion of such rare T cells would provide enough fighters for an effective immune response and enough antigen-experienced cells for memory. We show here that human thymopoiesis releases a large population of clustered CD8+ T cells harboring α/β paired TCRs that (i) have high generation probabilities and (ii) a preferential usage of some V and J genes, (iii) which CDR3 are shared between individuals, and (iv) can each bind and be activated by multiple unrelated viral peptides, notably from EBV, CMV, and influenza. These polyspecific T cells may represent a first line of defense that is mobilized in response to infections before a more specific response subsequently ensures viral elimination. Our results support an evolutionary selection of polyspecific α/β TCRs for broad antiviral responses and heterologous immunity.
