title: Transcriptionally abundant major histocompatibility complex class I alleles are fundamental to nonhuman primate simian immunodeficiency virus-specific CD8+ T cell responses.
abstract: Simian immunodeficiency virus (SIV)-infected macaques are the preferred animal model for human immunodeficiency virus (HIV) vaccines that elicit CD8(+) T cell responses. Unlike humans, whose CD8(+) T cell responses are restricted by a maximum of six HLA class I alleles, macaques express up to 20 distinct major histocompatibility complex class I (MHC-I) sequences. Interestingly, only a subset of macaque MHC-I sequences are transcriptionally abundant in peripheral blood lymphocytes. We hypothesized that highly transcribed MHC-I sequences are principally responsible for restricting SIV-specific CD8(+) T cell responses. To examine this hypothesis, we measured SIV-specific CD8(+) T cell responses in MHC-I homozygous Mauritian cynomolgus macaques. Each of eight CD8(+) T cell responses defined by full-proteome gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay were restricted by four of the five transcripts that are transcriptionally abundant (>1% of total MHC-I transcripts in peripheral blood lymphocytes). The five transcriptionally rare transcripts shared by these animals did not restrict any detectable CD8(+) T cell responses. Further, seven CD8(+) T cell responses were defined by identifying peptide binding motifs of the three most frequent MHC-I transcripts on the M3 haplotype. Combined, these results suggest that transcriptionally abundant MHC-I transcripts are principally responsible for restricting SIV-specific CD8(+) T cell responses. Thus, only a subset of the thousands of known MHC-I alleles in macaques should be prioritized for CD8(+) T cell epitope characterization.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin—Madison, Madison, Wisconsin 53706, USA.
authors.forename: Melisa L
authors.initials: ML
authors.lastname: Budde
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Lhost
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Ericka A
authors.initials: EA
authors.lastname: Becker
authors.forename: Charles M
authors.initials: CM
authors.lastname: Burns
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.forename: Julie A
authors.initials: JA
authors.lastname: Karl
authors.forename: Roger W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Bimber
authors.forename: Guang Lan
authors.initials: GL
authors.lastname: Zhang
authors.forename: William
authors.initials: W
authors.lastname: Hildebrand
authors.forename: Vladimir
authors.initials: V
authors.lastname: Brusic
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D008251:Macaca; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D015395:Histocompatibility Antigens Class I