title: Dominant clonotypes within HIV-specific T cell responses are programmed death-1high and CD127low and display reduced variant cross-reactivity.
abstract: HIV epitope-specific T cell responses are often comprised of clonotypic expansions with distinct functional properties. In HIV(+) individuals, we measured programmed death-1 (PD-1) and IL-7Rα expression, MHC class I tetramer binding, cytokine production, and proliferation profiles of dominant and subdominant TCR clonotypes to evaluate the relationship between the composition of the HIV-specific T cell repertoire and clonotypic phenotype and function. Dominant clonotypes are characterized by higher PD-1 expression and lower C127 expression compared with subdominant clonotypes, and TCR avidity positively correlates with PD-1 expression. At low peptide concentrations, dominant clonotypes fail to survive in culture. In response to stimulation with peptides representing variant epitopes, subdominant clonotypes produce higher relative levels of cytokines and display greater capacity for cross-recognition compared with dominant clonotypes. These data indicate that dominant clonotypes within HIV-specific T cell responses display a phenotype consistent with ongoing exposure to cognate viral epitopes and suggest that cross-reactive, subdominant clonotypes may retain greater capacity to suppress replication of viral variants as well as to survive in the absence of strong antigenic signaling.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Conrad
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramalingam
authors.forename: Rita M
authors.initials: RM
authors.lastname: Smith
authors.forename: Louise
authors.initials: L
authors.lastname: Barnett
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Lorey
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.forename: Brenna C
authors.initials: BC
authors.lastname: Simons
authors.forename: Shanmugalakshmi
authors.initials: S
authors.lastname: Sadagopal
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer-Olson
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000276:immunology*; D002999:Clone Cells / Q000473:pathology / Q000821:virology; D003429:Cross Reactions / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology*
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018984:Epitopes, T-Lymphocyte; D053699:Interleukin-7 Receptor alpha Subunit; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell