title: Immunodominance of HIV-1 specific CD8+ T-cell responses is related to disease progression rate in vertically infected adolescents.
abstract: BACKGROUND
  HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate.
  
  
  RESULTS
  In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups.
  
  
  CONCLUSIONS
  Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sharp
authors.forename: Christian B
authors.initials: CB
authors.lastname: Willberg
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kuebler
authors.forename: Jacob
authors.initials: J
authors.lastname: Abadi
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Fennelly
authors.forename: Joanna
authors.initials: J
authors.lastname: Dobroszycki
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Wiznia
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenberg
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D015550:Cell Degranulation; D002454:Cell Differentiation / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013045:Species Specificity; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016207:Cytokines; D006680:HLA Antigens; D016056:Immunodominant Epitopes; D010455:Peptides; D054301:gag Gene Products, Human Immunodeficiency Virus