title: Differential MHC class I expression in distinct leukocyte subsets.
abstract: BACKGROUND
  MHC class I proteins are partly responsible for shaping the magnitude and focus of the adaptive cellular immune response. In humans, conventional wisdom suggests that the HLA-A, -B, and -C alleles are equally expressed on the majority of cell types. While we currently have a thorough understanding of how total MHC class I expression varies in different tissues, it has been difficult to examine expression of single MHC class I alleles due to the homogeneity of MHC class I sequences. It is unclear how cDNA species are expressed in distinct cell subsets in humans and particularly in macaques which transcribe upwards of 20 distinct MHC class I alleles at variable levels.
  
  
  RESULTS
  We examined MHC gene expression in human and macaque leukocyte subsets. In humans, while we detected overall differences in locus transcription, we found that transcription of MHC class I genes was consistent across the leukocyte subsets we studied with only small differences detected. In contrast, transcription of certain MHC cDNA species in macaques varied dramatically by up to 45% between different subsets. Although the Mafa-B134:02 RNA is virtually undetectable in CD4+ T cells, it represents over 45% of class I transcripts in CD14+ monocytes. We observed parallel MHC transcription differences in rhesus macaques. Finally, we analyzed expression of select MHC proteins at the cell surface using fluorescent peptides. This technique confirmed results from the transcriptional analysis and demonstrated that other MHC proteins, known to restrict SIV-specific responses, are also differentially expressed among distinct leukocyte subsets.
  
  
  CONCLUSIONS
  We assessed MHC class I transcription and expression in human and macaque leukocyte subsets. Until now, it has been difficult to examine MHC class I allele expression due to the similarity of MHC class I sequences. Using two novel techniques we showed that expression varies among distinct leukocyte subsets of macaques but does not vary dramatically in the human cell subsets we examined. These findings suggest pathogen tropism may have a profound impact on the shape and focus of the MHC class I restricted CD8+ T cell response in macaques.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, 53706 Wisconsin, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.forename: Roger W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: Simon M
authors.initials: SM
authors.lastname: Lank
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Bimber
authors.forename: Julie A
authors.initials: JA
authors.lastname: Karl
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Lhost
authors.forename: Oriana E
authors.initials: OE
authors.lastname: Hawkins
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kunstman
authors.forename: Karl W
authors.initials: KW
authors.lastname: Broman
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
authors.forename: William H
authors.initials: WH
authors.lastname: Hildebrand
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
mesh_terms: D000483:Alleles; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005786:Gene Expression Regulation; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D008251:Macaca; D014158:Transcription, Genetic
chemical_list: D015395:Histocompatibility Antigens Class I