Project description:The extreme polymorphisms of human leukocyte antigen (HLA) class I proteins result in structural variations in their peptide binding sites to achieve diversity in antigen presentation. External factors could independently constrict or alter HLA class I peptide repertoires. Such effects of the assembly factor tapasin were assessed for HLA-B*44:05 (Y116) and a close variant, HLA-B*44:02 (D116), which have low and high tapasin dependence, respectively, for their cell surface expression. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with C-terminal tryptophans and higher predicted affinities are preferentially selected by tapasin, coincident with reduced frequencies of peptides with other C-terminal amino acids, including leucine. Comparisons of the HLA-B*44:05 and HLA-B*44:02 peptidomes indicate the expected structure-based alterations near the peptide C-termini, but also C-terminal amino acid frequency and predicted affinity changes among the unique and shared peptide groups for B*44:02 and B*44:05. Overall, these findings indicate that the presence of tapasin and the tapasin-dependence of assembly alter HLA class I peptide binding preferences at the peptide C-terminus. The particular C-terminal amino acid preferences that are altered by tapasin are expected to be determined by the intrinsic peptide binding specificities of HLA class I allotypes. Additionally, the findings suggest that tapasin deficiency and reduced tapasin dependence expand the permissive affinities of HLA class I bound peptides, consistent with prior findings that HLA class I allotypes with low tapasin dependence have increased breadth of CD8+ T cell epitope presentation and are more protective in HIV infections.
Project description:Sorted cells from bone marrow and rectal mucosa of SIV-infected rhesus macaques were analyzed for expression of factors associated with plasma cell recruitment, adhesion, or maintenance mRNA expression anaylsis was performed on 16 CD2-CD19-CD20-HLA-DR+ and 16 CD2-CD19-CD20-HLA-DR- bone marrow cells, and 7 CD2-CD19-CD20-HLA-DR+ and 3 CD2-CD19-CD20-HLA-DR- rectal cells using a custom CodeSet produced by NanoString Technologies containing 44 niche factor genes of interst, 12 cell-type specific genes, and 9 reference genes identified in Genevestigator.
Project description:Clear cell renal cell carcinoma comprises two dominant subtypes, ccA and ccB, with gender disparity providing additional disease information. A third minor subgroup has distinct expression profiles consistent with von Hippel-Lindau wild type status and displays variant histology features. 44 new tumor samples and six large, publicly available, ccRCC gene expression databases were identified that cumulatively provided data for 480 tumors for metaanalysis via meta-array compilation.