RESUMEN
Different human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccine vectors expressing the same viral antigens can elicit disparate T-cell responses. Within this spectrum, replicating variable vaccines, like SIVmac239Δnef, appear to generate particularly efficacious CD8(+) T-cell responses. Here, we sequenced T-cell receptor ß-chain (TRB) gene rearrangements from immunodominant Mamu-A 01-restricted Tat(28-35)SL8-specific CD8(+) T-cell populations together with the corresponding viral epitope in four rhesus macaques during acute SIVmac239Δnef infection. Ultradeep pyrosequencing showed that viral variants arose with identical kinetics in SIVmac239Δnef and pathogenic SIVmac239 infection. Furthermore, distinct Tat(28-35)SL8-specific T-cell receptor (TCR) repertoires were elicited by SIVmac239Δnef compared to those observed following a DNA/Ad5 prime-boost regimen, likely reflecting differences in antigen sequence stability.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Productos del Gen nef/inmunología , Inmunización Secundaria/métodos , Vacunas contra el SIDAS/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Vacunación/métodos , Adenoviridae/genética , Adenovirus Humanos , Animales , Portadores de Fármacos/administración & dosificación , Vectores Genéticos , Secuenciación de Nucleótidos de Alto Rendimiento , Macaca mulatta , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Vacunas contra el SIDAS/administración & dosificación , Subgrupos de Linfocitos T/inmunología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunologíaRESUMEN
Rhesus macaque models have been instrumental in the development and testing of vaccines before human studies and have provided fundamental insights into the determinants of immune efficacy in a variety of infectious diseases. However, the characterization of antigen-specific T-cell receptor (TCR) repertoires during adaptive immune responses in these models has earlier relied on human TCR gene assignments. Here, we extracted and characterized TCR beta-chain (TRB) genes from the recently sequenced rhesus macaque genome that are homologous to the human TRB genes. Comparison of the rhesus macaque TRB genes with the human TRB genes showed an average best match similarity of 92.9%. Furthermore, we confirmed the usage of most rhesus macaque TRB genes by expressed TCRbeta sequences within epitope-specific TCR repertoires. This primary description of the rhesus macaque TRB genes will provide a standardized nomenclature and enable better characterization of TCR usage in studies that use this species.