The consensus motifs of HLA-Cw3, -Cw4, -Cw6, and -Cw7 ligands were determined by pool sequencing. Together with information obtained by sequencing of some prominent individual peptides, the results indicate the following: (i) all four HLA-C molecules are associated with peptides. (ii) These peptides adhere to allele-specific motifs that are similar to those of to HLA-A or -B molecules; they have a preferred length of nine amino acids and an anchor residue at the C terminus. (iii) All four HLA-C molecules analyzed exhibit related peptide motifs, although each allelic product shows individual characteristics in fine specificity. (iv) Processing and origin of peptides appear not to be different from that of other class I molecules. (v) No obvious difference at C-terminal position 9 was present in the peptides isolated from the two dimorphic variants of HLA-C that determine dominant resistance to natural killer NK1-specific cells (HLA-Cw4, -Cw6) or to NK2-specific cells (HLA-Cw3, -Cw7) and that differ in two residues in or near the pocket at position 9.

Background: The role of angiogenesis in the pathogenesis of renal cell carcinoma is well recognized, however, the influence of tumor cells in this activity has not yet been fully clarified. The aim of this study was to analyze the expression of hypoxia inducible factor-1α (HIF-1α), a regulatory factor of angiogenic switch, in comparison to vascular endothelial growth factor A and C (VEGF-A and VEGF-C), recognized to be involved in blood and lymph vessel neoangiogenesis, with potential association in the prognosis of patients with renal cell carcinoma. Methods: Ninety-four patients with diagnosis of clear cell renal cell carcinomas (CCRCC), all clinicopathological characteristics and overall survival were unrolled in this study. Immunohistochemicaly VEGF-A, VEGF-C, HIF-1α and Ki67 were detected on tumor cells and the staining was performed on tissue microarrays (TMA). The staining was evaluated as a percentage of cytoplasmic or nuclear positive tumor cells. Results: Variable expression of all three proteins was confirmed. Both angiogenic factors demonstrated perimembranous or diffuse cytoplasmic staining, with diffuse pattern positively associated (p < 0.001). Nuclear HIF-1α expression (nHIF-1α) showed inverse correlation with diffuse cytoplasmic VEGF-A (p = 0.002) and VEGF-C (p = 0.053), while cytoplasmic HIF-1α expression (cHIF-1α) showed positive correlation with diffuse staining of both angiogenic factors (p < 0.001; p < 0.001, respectively). In comparison to clinicopathological characteristics, a higher nuclear grade (p = 0.006; p < 0.001, respectively), larger tumor size (p = 0.009; p = 0.015, respectively), higher stage (p = 0.023; p = 0.027, respectively) and shorter survival (p = 0.018; p = 0.024, respectively) were associated with overexpression of cHIF-1α and diffuse cytoplasmic VEGF-A expression. In contrary, overexpression of nHIF-1α was associated with better diagnostic parameters i.e. lower nuclear grade (p = 0.006), smaller tumor size (p = 0.057), and longer survival (p = 0.005). Conclusion: Overexpression of VEGF-A and cHIF-1α in tumor cells highlights a more aggressive subtype of CCRCC that might have some clinical implications. The significance of nHIF-1α expression associated with better differentiated tumors should be further elucidated.